atrial-natriuretic-factor and Hypertension--Renovascular

Atrial natriuretic peptide is a recently discovered cardiac hormone with natriuretic, vasodilatory and hypotensive activities. The role of this hormone in the pathophysiology of hypertension is of particular interest. In contrast to an earlier concept, a deficiency of the atrial peptide could not be found in animal models of hypertension or in patients. ANP plasma levels were elevated in SHR with accelerated hypertension, in salt-sensitive Dahl rats, in rats with DOCA-salt-hypertension and in animals with renovascular hypertension. Elevated ANP levels under these conditions can be explained by an expansion of the intravascular volume or by an elevated atrial wall stretch induced by the hypertension itself. In patients with primary hypertension, plasma levels of the peptide are raised in some patients and are normal in others. Plasma ANP levels correlate with age, blood pressure and signs of left ventricular hypertrophy. A negative correlation is described between ANP and renin. Measurement of plasma ANP levels does not allow a differentiation between primary and secondary forms of hypertension. Elevated ANP levels are also found in primary hyperaldosteronism and in renal failure. Stimulation of ANP secretion by physical exercise and dietary salt loading is maintained in hypertension. Infusion of 1-28-hANP leads to a reduction in systemic arterial pressure in normotensives and hypertensives. The natriuresis induced by exogenous ANP is more pronounced in hypertensives. Stimulation of endogenous ANP secretion does not prevent the rise in blood pressure possibly due to a reduction in ANP receptors in target tissues.

Topics: Acromegaly; Animals; Atrial Natriuretic Factor; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Kidney Failure, Chronic; Male; Rats; Rats, Inbred Strains

Atrial natriuretic factor (ANF) antagonizes vasoconstriction induced by numerous smooth muscle agonists and also lowers blood pressure in intact animals. ANF has particularly marked relaxant effects on angiotensin II-contracted vessels in vitro. Sensitivity to the blood pressure-lowering effect of ANF in vivo appears to be enhanced in renin-dependent models of renovascular hypertension compared with other experimental hypertensive models. The depressor action of low, possibly physiological doses of ANF in two-kidney, one-clip Goldblatt rats is due to a decrease in total peripheral resistance. On the other hand, high doses of ANF can lower cardiac output, particularly in volume-expanded models such as deoxycorticosterone-salt hypertension. ANF markedly inhibits renin secretion in intact animals, probably via increased glomerular filtration rate and load of sodium chloride to the macula densa. This effect is masked when renal perfusion is impaired (e.g., via unilateral renal artery constriction), in which case ANF may stimulate renin secretion slightly. ANF also reduces plasma aldosterone in vivo and inhibits basal and agonist-induced aldosterone release from isolated adrenal cortical cells. This effect appears to be especially marked for angiotensin-induced aldosterone production in vivo and in vitro. These findings indicate that ANF has potentially important interactions with the renin-angiotensin-aldosterone system and suggest a role for ANF in the homeostatic control of blood pressure as well as of extracellular fluid volume.

Topics: Adrenal Glands; Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Glomerular Filtration Rate; Hypertension, Renovascular; Kidney; Mineralocorticoid Receptor Antagonists; Renin; Renin-Angiotensin System; Saralasin; Vascular Resistance; Vasoconstriction

To sum up, the endocrine analysis of human hypertension, tracing the renin system patterns, has provided a convincing body of data revealing and defining the biochemical heterogeneity of human hypertension. The heterogeneity, and the ability to differentiate it by the study of renin, embraces the major category that we call essential hypertension, which brackets at least 85% of all hypertension patients. This spectrum of biochemical heterogeneity is manifested physiologically by two different forms of vasoconstriction. One form is renin-mediated vasoconstriction, signified by the finding of a medium or high plasma renin activity and corrected by antirenin surgical or pharmacologic means. Toward the other end of the spectrum, revealed by the finding of low plasma renin, a sodium-volume-induced form of vasoconstriction operates. This appears to involve abnormal calcium metabolism and can also be characterized by measurable changes in serum ionized calcium values. With the development of newer and more specific antihypertensive agents with actions that appear to be rather specific against a particular vasoconstriction mechanism, new patterns of treatment are emerging that are preferable to the undiscriminating protocols of diuretic-oriented stepped care. The beta blockers or the CEIs can now be considered as the first pharmacological step against high- or medium-renin hypertensive states. The prescription of diuretics as the first step against the low-renin state can now be weighed against a more rational physiologic attack involving the probably safer, less troublesome, and more specific calcium-channel blocking drugs and also by the less potent alpha-adrenergic blockers. These latter two types of agents may exhibit finer marksmanship than do diuretics in opposing the etiology of low-renin hypertension, for there is growing reason to believe that sodium-volume-mediated vasoconstriction is related to abnormal calcium influx and possibly to abnormal alpha-adrenergic traffic.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Calcium; Enzyme Precursors; Humans; Hypertension; Hypertension, Renovascular; Renin; Renin-Angiotensin System; Vasoconstriction

Atrial natriuretic factor (ANF) is a recently discovered peptide present in secretory granules specifically found in atrial muscle cells. Multiple structurally related peptides have been isolated from atrial tissues, all of which are derived from a common 152-amino-acid precursor. ANF induces profound natriuresis and diuresis in experimental animals and also causes relaxation of precontracted vascular smooth muscle. ANF has striking renal hemodynamic actions (most consistently an increased glomerular filtration rate), which probably explain its natriuretic effects. ANF also can inhibit renin secretion in vivo and causes direct inhibition of basal and stimulated aldosterone production. It lowers arterial blood pressure, probably reflecting in part its vasorelaxant actions, and this effect is particularly marked in renin-dependent (and possibly other vasoconstricted) models of hypertension. Although the exact structure and regulation of the presumed circulating form(s) of ANF remain to be clarified, available information suggests that it may be a new, previously unrecognized factor in the regulation of fluid volume and renal and cardiovascular function.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Blood Pressure; Chemical Phenomena; Chemistry; Hemodynamics; Humans; Hypertension, Renovascular; In Vitro Techniques; Kidney; Muscle Contraction; Muscle, Smooth, Vascular; Perfusion; Protein Precursors; Renin-Angiotensin System

The renin-angiotensin-aldosterone system plays a major role in renovascular hypertension, but the relationship between renin release and the renal fractional extraction of atrial natriuretic peptide (ANP) in this condition is not well defined. We measured ANP levels in the renal veins and aortas of 49 untreated hypertensive patients studied under standardized conditions immediately before renal angiography. Twenty-one patients had renal artery stenosis, 13 of which were unilateral and 8 bilateral. Five of the 13 patients with unilateral renal artery stenosis had an elevated renin ratio (> or = 1.5). Patients with renal artery stenosis were older (P < .01) and had higher systolic pressures (P < .05) than patients with essential hypertension. Arterial levels of ANP were significantly higher in patients with unilateral or bilateral renal artery stenosis than in patients with essential hypertension (P < .05). Patients with hypertension and left ventricular hypertrophy had significantly higher arterial ANP levels than those with no hypertrophy (40 versus 26 pmol/L, P < .05), but in patients with renal artery stenosis, arterial ANP levels were similar in those with or without hypertrophy. Renal venous ANP levels were significantly higher in stenotic than in normal kidneys. Moreover, in unilateral renal artery stenosis, stenotic kidneys of patients with an elevated renin ratio (stenotic kidney/contralateral kidney > or = 1.5) had a significantly higher renal venous ANP level than stenotic kidneys of patients with normal renin ratio (30 versus 17 pmol/L, P < .05). However, the median fractional extraction of ANP was similar, around 0.50 (range, 0 to 0,83), in normal kidneys of hypertensive patients and in stenotic and contralateral kidneys of patients with renal artery stenosis. A significant inverse correlation between arterial ANP and renal venous active plasma renin concentration was found for normal kidneys (r= -.62, P < .01) of hypertensive patients without hypertrophy. However, for stenotic kidneys, no such relationship was apparent. A significant correlation between arterial ANP and the arteriovenous difference of ANP (r = +.92, P < .001) was found. This relationship was similar for normal and stenotic kidneys. In conclusion, an inverse relationship between arterial ANP and renal venous active plasma renin concentration exists in normal kidneys of essential hypertensive patients without left ventricular hypertrophy. Furthermore, data of ANP extraction thro

Topics: Adult; Aged; Angiotensin II; Atrial Natriuretic Factor; Female; Humans; Hypertension; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Kidney; Male; Middle Aged; Radiography; Renal Artery; Renal Veins; Renin

In the present study, the change in secretion of atrial natriuretic peptide (ANP) from the atria was defined in hypertension accompanied by ventricular hypertrophy and increased synthesis of ANP. To identify the change of the secretion and mechanisms involved, experiments were performed in isolated perfused beating atria from sham-operated normotensive and renovascular hypertensive rats. Expression of ANP, natriuretic peptide receptor (NPR)-C, components of the renin-angiotensin system, and muscarinic signaling pathway was measured in cardiac tissues. Basal levels of ANP secretion and acetylcholine (ACh)- and stretch-induced activation of ANP secretion were suppressed in the atria from hypertensive compared with normotensive rats. ACh increased ANP secretion via M

Topics: Animals; Atrial Natriuretic Factor; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Heart Atria; Heart Ventricles; Hypertension, Renovascular; Male; Rats; Rats, Sprague-Dawley; Receptors, Angiotensin; Receptors, Muscarinic

Angiotensin II (Ang II) is an important inflammatory mediator. Ang II induces cyclooxygenase-2 (COX-2) expression and prostaglandin F2α release followed by cardiac hypertrophy. Inhibition of COX-2 may modulate high blood pressure but controversy still exists. The aim of this study was to determine the role of COX-2 in the regulation of blood pressure and to define the mechanisms in two kidney one-clip hypertensive (2K1C) rats. Chronic treatment with nimesulide or NS-398 (5 mg/kg/day) for 3 weeks lowered high blood pressure and cardiac hypertrophy with decreased expression levels of cardiac hypertrophy markers [atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP)], Ang type 1 receptor, urotensin II, and urotensin II receptor in 2K1C rats. Plasma level of ANP was markedly increased and plasma levels of Ang II and aldosterone were decreased by treatment with nimesulide or NS-398. In both in vitro and in vivo experiments, nimesulide or NS-398 augmented ANP release in 2K1C rats. The inhibitory effect of NS-398 on blood pressure was attenuated by the pretreatment with natriuretic peptide receptor-A (NPR-A) antagonist (A71915, 30 μg/kg/day). These results suggest that chronic treatment with nimesulide or NS-398 attenuated hypertension and cardiac hypertrophy partly through ANP release in 2K1C rats.

Topics: Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiomegaly; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Gene Expression Regulation, Neoplastic; Humans; Hypertension, Renovascular; Natriuretic Peptide, Brain; Nitrobenzenes; Rats; Sulfonamides

The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Hypertension, Renovascular; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Natriuretic Peptide, Brain; Receptors, Atrial Natriuretic Factor; Renin; Renin-Angiotensin System; Surgical Instruments; Vasoconstriction; Vasodilation

The aim of the present study was to perform immunohistochemical and ultrastructural analysis of gastrin-, synaptophysin (SY)- and atrial natriuretic peptide (ANP)-positive cells in the pylorus of "two kidney, one clip" (2K1C) renovascular hypertension model in rats.. In order to identify neuroendocrine (NE) cells, immunohistochemical reactions were performed with the use of specific antibodies against gastrin, SY and ANP. Gastric NE cells were also examined using an electron microscope.. The present study revealed a twofold increase in the number of gastrin- and SY-positive cells and a significant decrease in the number of ANP-immunoreactive (IR) cells in the pyloric mucosa of 2K1C rats. Test results obtained with an electron microscope confirmed a change in the activity of the stomach endocrine cells of hypertensive rats.. Immunohistochemical and ultrastructural investigations demonstrated the impact of renovascular hypertension on the neuroendocrine system in the rat stomach. The changes in the total number and ultrastructure of DNES cells proved their undeniable role in the modulation of gastric dysfunction, as a consequence of deregulation of homeostasis-maintaining systems.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Disease Models, Animal; Enteroendocrine Cells; Gastric Mucosa; Gastrins; Hypertension, Renovascular; Male; Pylorus; Rats, Wistar; Synaptophysin

The NADPH oxidases (Noxes) are a family of ROS (reactive oxygen species)-generating enzymes which play a critical role in the development of cardiac remodeling associated with heart failure. The Noxes of their catalytic isoforms include multiple homologues in cardiovascular cells with wide range tissue distribution. It is still unclear which Noxes represent the major enzymatic source of ROS in the heart and play a predominant role in cardiac hypertrophy. In this study we investigated the differential expression changes of NAD(P)H oxidase P47phox isoform and Nox homologues in left ventricle and the effects of atorvastatin on cardiac remodeling in two-kidney two-clip(2K2C) hypertensive rats. The mRNA and protein expression of Nox2, Nox4 and P47phox showed a sustained increase at 4, 8, 12 weeks after surgery in 2K2C rats. Administration of atorvastatin attenuated cardiac dysfunction, hypertrophy and fibrosis of 2K2C rats. However, atorvastatin treatment had no effects on BP regulation. Further studies revealed that atorvastatin inhibited the increased expression of Nox2, Nox4, P47phox as well as 02"- production in 2K2C hypertensive rats. These findings indicate that Nox2, Nox4 and P47phox play a crucial role in the development of cardiac remodeling in the 2K2C hypertensive rats. Atorvastatin, independent of BP control, exerts anti-remodeling effects partially by inhibition of NAD(P)H oxidase-mediated cardiac oxidative stress.

Topics: Animals; Atorvastatin; Atrial Natriuretic Factor; Blotting, Western; Fibrosis; Hemodynamics; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension, Renovascular; Isoenzymes; Male; Membrane Glycoproteins; Myocardium; Myosin Heavy Chains; NADPH Oxidase 2; NADPH Oxidase 4; NADPH Oxidases; Pyrroles; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Hemodynamic parameters and natriuretic peptide levels were evaluated in cardiac hypertrophy produced by sequentially applied renovascular (RV) and deoxycorticosterone acetate-salt (DS) models of hypertension. We studied hypertensive rats by RV or DS treatment at 2 and 4 wk, as well as by the combination of 2 wk of each treatment in an inverse sequence: RV 2 wk/DS 2 wk (RV2/DS2) and DS 2 wk/RV 2 wk (DS2/RV2). The in vivo cardiac function, interstitial fibrosis, and synthesis and secretion of types A (ANP) and B (BNP) natriuretic peptides were monitored in hypertensive models compared with their corresponding sham (Sh2, Sh4). There were no differences in relaxation parameters among RV or DS groups and combined treatments. Left ventricular +dP/dt(max) increased only in RV4 (P < 0.01 vs. Sh4), and this increase was abolished in RV2/DS2. Interstitial collagen concentration increased after 4 wk in both RV4 and RV2/DS2 groups. Although there were no changes in collagen concentration in either DS2 or DS4 groups, clipping after 2 wk of DS (DS2/RV2) remarkably stimulated interstitial fibrosis (P < 0.01 vs. DS2). Plasma BNP increased in RV treatment at 4 wk (P < 0.001 vs. Sh4), but not in DS. Interestingly, RV applied after the 2 wk of DS treatment induced a marked increase in BNP levels (P < 0.001 vs. Sh4). In this regard, plasma BNP appears to be a reliable indicator of pressure overload. Our results suggest that the second stimulus of mechanical overload in combined models of hypertension determines the evolution of hypertrophy and synthesis and secretion of ANP and BNP.

Topics: Animals; Atrial Natriuretic Factor; Biomechanical Phenomena; Blood Pressure; Collagen; Desoxycorticosterone; Disease Models, Animal; Hypertension; Hypertension, Renovascular; Male; Natriuretic Peptide, Brain; Natriuretic Peptides; Rats; Rats, Sprague-Dawley; Ventricular Function, Left

The system of cardiac natriuretic peptides (NP) is a very important factor opposing the effects of the rennin-angiotensin-aldosterone system (RAAS), sympathoadrenal system and vasopressin to reduce blood pressure. In the present study, we analyzed the release of atrial and brain natriuretic peptides in the myocytes of the right atrium in rats by the quantitative morphometric method using double immunocytochemical labeling of atrial granules comprising NP in vasorenal hypertension induced by the renal artery ligation. The decrease in the total amount of secretory granules in atrium myocytes by 18% was detected on the 30th day after the operation. The number of the A-type granules was reduced by 53%, and the number of B-type granules was increased by 64% in comparison with the intact animals. Our data indicate activation of NP secretion in vasorenal hypertension. The results suggest that high arterial pressure might be explained by reduced expression of NP receptors in this pathology.

Topics: Animals; Atrial Natriuretic Factor; Cytoplasmic Granules; Heart Atria; Hypertension, Renovascular; Immunohistochemistry; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats; Rats, Inbred Strains

We have previously shown the augmented levels of Gialpha-2 and Gialpha-3 proteins (isoforms of inhibitory guanine nucleotide regulatory protein (G-protein)), and not of Gsalpha, in the hearts and aortas of spontaneously and experimentally induced hypertensive rats. The increased expression of Gialpha and blood pressure was restored toward WKY levels by captopril treatment, suggesting a role for angiotensin (Ang) II in the enhanced expression of Gialpha protein and blood pressure. This study was undertaken to investigate whether 1 kidney 1 clip (1K-1C) hypertensive rats that exhibit enhanced levels of Ang II also express enhanced levels of Gialpha proteins. Aortas from 1K-1C hypertensive rats were used. The expression of G-proteins was determined at protein levels with immunoblotting techniques, using specific antibodies for different isoforms of G-proteins. The levels of Gialpha-2 and Gialpha-3 proteins were significantly higher in aortas from 1K-1C hypertensive rats than in control rats; Gsalpha levels were unchanged. The inhibitory effect of low concentrations of guanosine 5'-[gamma-thio]triphosphate (GTPgammaS) on forskolin (FSK)-stimulated adenylyl cyclase (AC) activity was significantly enhanced in aortas from 1K-1C hypertensive rats; the inhibitory effect of C-ANP(4-23), which specifically interacts with the atrial natriuretic peptide (ANP)-C receptor, and Ang II on AC was attenuated. GTPgammaS, isoproterenol, glucagon, NaF, and FSK stimulated the AC activity in aortas from control and hypertensive rats to varying degrees; however, the stimulations were significantly lower in hypertensive rats than in control rats. These data suggest that aortas from 1K-1C hypertensive rats exhibit enhanced expression of Gialpha proteins and associated functions.

Topics: Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Angiotensin II; Animals; Antihypertensive Agents; Aorta; Atrial Natriuretic Factor; Captopril; Colforsin; Dose-Response Relationship, Drug; Glucagon; GTP-Binding Protein alpha Subunits, Gi-Go; Guanosine 5'-O-(3-Thiotriphosphate); Hypertension, Renovascular; Immunoblotting; Isoproterenol; Peptide Fragments; Rats; Rats, Sprague-Dawley; Renal Artery Obstruction; Signal Transduction; Sodium Fluoride; Time Factors

The aim of this study was to investigate the effect of ketamine on the endocrine and lipid metabolic status of the renal-banded animals.. Forty male rats were randomly divided into four groups. Group A served as control, Group B animals received ketamine intraperitoneally at a dose of 100 mg kg(-1), Group C was submitted to 2-kidney 1-clip experimental hypertension and Group D received ketamine as above, as well as being submitted to renal artery clipping. Atrial natriuretic peptide, angiotensin II and free fatty acid concentrations were measured in serum. In addition, adipose tissue lipoprotein lipase activity and angiotensin II content were determined, while the left ventricular weight relative to body weight was used as a cardiac hypertrophy index.. In renal-banded rats (Groups C and D) serum atrial natriuretic peptide, free fatty acid and angiotensin II concentrations as well as ventricular weight were increased, while adipose tissue lipoprotein lipase activity was lower than in control animals (Groups A and B). Ketamine administration did not influence angiotensin II concentrations either in normal (Group B) or banded rats (Group D). Ketamine increased serum atrial natriuretic peptide and free fatty acid concentrations only in normal animals (Group B). It had no influence on adipose tissue lipoprotein lipase activity either in normal (Group B) or banded animals (Group D). Adipose angiotensin II content did not differ between the four groups.. Ketamine increased the atrial natriuretic peptide and free fatty acid concentration in normal rats. In 2-kidney 1-clip animals, ketamine did not elicit an additional response of serum atrial natriuretic peptide or free fatty acids levels. Its contribution to these factors was not significant.

Topics: Adipose Tissue; Anesthetics, Dissociative; Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Fatty Acids, Nonesterified; Hypertension, Renovascular; Ketamine; Kidney; Lipid Metabolism; Lipoprotein Lipase; Male; Rats; Rats, Wistar; Renal Artery; Renin-Angiotensin System

To investigate the expression of A-type atrial natriuretic peptide receptor (ANPR-A) in the kidneys of renovascular hypertension rats and evaluate the significance of the expression.. The rat model of renovascular hypertension was produced by constricting one lateral renal artery. After the renal artery being constricted for 4 weeks and 8 weeks, the systolic BP of rats was measured with a manometer using the tail-cuff method. Then, the expression of ANPR-A was respectively detected by immunohistochemical technique in the kidneys of the two-kidney, one-clip (2K1C) rats, and the expression level of ANPR-A was semi-quantitatively measured by Mias-2000 computer image analyzer.. At 4 weeks after the artery-constricted operation,the expression of ANPR-A increased significantly in 2K1C hypertensive rat glomeruli and decreased significantly in renal tubules, compared with control (P<0.01), but there was no marked change in medullar collecting tubules. At 8 weeks after the artery-constricted operation, the expression of ANPR-A decreased significantly in 2K1C hypertensive rat renal tubules and medullar collecting tubules, compared with control (P<0.01); however, there was weak expression in glomeruli, and no statistically significant difference was seen when compared with control (P>0.05).. The expression of ANPR-A decreased significantly in kidney tissues of renovascular

Topics: Animals; Atrial Natriuretic Factor; Hypertension, Renovascular; Kidney; Male; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor

Renal excretion in experimental hypertensive rats implanted with encapsulated human atrial natriuretic peptide (hANP)-producing cells is circadian periodic. Chinese hamster ovary (CHO) cells transfected with the plasmid hANP-cDNA were encapsulated in biocompatible polycaprolactone capsules for intraperitoneal implantation into two-kidney, one-clip (2K1C) hypertensive rats. During a 12:12 light-dark cycle, as compared to control CHO cells, the implantation of encapsulated hANP-producing CHO cells was associated with an increase in the net excretion of water, sodium and potassium, and with a reversal of the advanced circadian phases related to renovascular hypertension in 2K1C rats. The increase in blood pressure postimplantation was delayed, and increases in renal blood flow, glomerular filtration rate, sodium output, urinary excretion and urinary cyclic GMP concentrations were also found. Implantation of encapsulated hANP-producing cells affects circadian rhythms in kidney excretion functions of 2K1C rats, and may be useful for the treatment of cardiovascular disease.

Topics: Animals; Atrial Natriuretic Factor; Biocompatible Materials; CHO Cells; Circadian Rhythm; Cricetinae; Diuresis; Gene Expression; Genetic Therapy; Humans; Hypertension, Renovascular; Kidney; Male; Models, Animal; Natriuresis; Rats; Rats, Wistar; Transfection

A technique based on release of the human atrial natriuretic peptide (hANP) from plasmid hANP cDNA transfected Chinese hamster ovary (CHO) cells encapsulated in polycaprolactone (PCL)-capsules was used for a potential therapeutic approach to hypertension or congestive heart failure (CHF). The plasmid combining with hANP cDNA was transfected into CHO cells, and then encapsulated plasmid hANP cDNA transfected CHO cells were implanted into two-kidney, one-clip (2K1C) hypertensive rats intraperitoneally. The morphological changes, histological changes were investigated after the implantation of PCL-capsules in 2K1C hypertensive rats. The results showed that the implantation of encapsulated hANP-producing cells caused a significant delay of blood pressure (BP) increase after the encapsulated cells being implanted in 2K1C hypertensive rats. These effects were reflected morphologically by an attenuation of the glomerular sclerotic lesions, tubular damage and renal arterial thickening, comparing with control group. The plasma levels of hANP in 2K1C rats implanted with the PCL-capsules containing hANP-producing cells were higher than that of the control rats. These results demonstrated the usefulness of encapsulated hANP gene transfected cells as a new tool for hANP gene delivery in studying renovascular hypertension and cardiovascular diseases, thus implying the potential of using gene transfected cells as therapeutic agents in the treatment of cardiovascular diseases.

Topics: Animals; Atrial Natriuretic Factor; Capsules; Cell Transplantation; CHO Cells; Cricetinae; DNA, Complementary; Genetic Therapy; Humans; Hypertension, Renovascular; Kidney; Male; Plasmids; Rats; Rats, Wistar; Recombination, Genetic; Transfection; Transgenes

A study was designed to elucidate the mechanism of anti-hypertensive effects of danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed. The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of danshen extract for three weeks. These results suggest that danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Dose-Response Relationship, Drug; Hypertension, Renovascular; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Renin; Renin-Angiotensin System; Salvia miltiorrhiza; Water

Increased expression of the cardiac natriuretic peptides (NP), atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) is observed during chronic hemodynamic overload. The mechanisms underlying this process are not fully understood. In vitro, endothelin 1 (ET-1) is a powerful stimulator of cardiac NP and, therefore, has been assumed to be one possible mediator of increased NP gene expression following chronic pressure or volume overload. In the present work we investigated the possible role of ET-1 in mediating the observed upregulation of cardiac NP in two kidney-one clip (2K-1C) Goldblatt hypertensive rats treated for 6 weeks with the ET-1 type A (ET(A)) receptor subtype receptor antagonist ABT-627.. 2K-1C hypertension was induced in male Sprague-Dawley rats weighing 100-125 g by placing a silver clip (internal diameter 0.25 mm) around the left renal artery through a flank incision. The right kidney was left undisturbed. Sham operated rats underwent the same experimental procedures but no clip was placed on the left renal artery. ABT-627 was administered (10 mg/kg per day) in the drinking water for 6 weeks.. In hypertensive rats, ABT-627 prevented a further rise in blood pressure beginning at 3 weeks after clipping and reduced the ventricular hypertrophy observed at the end of the experiment. ET(A) blockade prevented enhanced NP gene expression in the right ventricle and partially prevented it in the left ventricle. No modifications in atrial NP gene expression were observed in either control or 2K-1C animals. ET(A) blockade decreased BNP circulating levels but did not affect ANF plasma levels in clipped rats. ABT-627 increased alpha-myosin heavy chain gene expression and decreased the abundance of the beta isoform transcript.. The results obtained in the present investigation show the participation of ET-1 in the increased expression of ventricular NP in 2K-1C renovascular hypertension and an apparent lack of effect of ET(A) blockade on atrial NP gene expression in both control and hypertensive animals thus showing that in vivo, atrial and ventricular NP gene expression are differentially regulated.

Topics: Analysis of Variance; Animals; Atrasentan; Atrial Natriuretic Factor; Blotting, Northern; Collagen; Endothelin Receptor Antagonists; Endothelin-1; Gene Expression Regulation; Heart Atria; Heart Ventricles; Hypertension, Renovascular; Male; Natriuretic Peptide, Brain; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; RNA, Messenger

The aim of our study was to clarify whether atrial (ANP) and brain (BNP) natriuretic peptides and the hypotensive peptide adrenomedullin (ADM) are regulated differently in the rat heart in the two-kidney, one-clip model of renovascular hypertension. We assessed messenger ribonucleic acid (mRNA) abundance and distribution of ANP, BNP and ADM in the ventricles and atria of rats after unilateral renal artery stenosis (clipping). Rats were clipped for 6 h or 1, 2 or 4 days and mRNA levels were assessed semiquantitatively in left and right atria and ventricles by RNase protection assay. Left ventricular BNP mRNA up-regulation (4.3-fold after 6 hours) preceded ANP up-regulation (4.5-fold after 1 day) and seemed to be transient, whereas ANP mRNA levels were still elevated at day 4 (2.4-fold vs. sham). The right ventricle and the atria did not participate in these responses. Despite the massive changes of natriuretic peptide mRNAs, ADM mRNA did not change in either the ventricles or the atria. In contrast to ANP and BNP mRNA, which predominate in atrial tissue, mRNA for adrenomedullin is equally distributed in ventricles and atria. Plasma levels of immunoreactive (ir)-ANP and ir-BNP changed in parallel with left ventricular mRNA levels. Our findings suggest that renovascular hypertension induced by clipping the renal artery leads to immediate, but independent, up-regulation of ANP and BNP mRNA in the left ventricle whereas adrenomedullin mRNA is not changed.

Topics: Adrenomedullin; Animals; Atrial Natriuretic Factor; Heart Atria; Heart Ventricles; Hypertension, Renovascular; Male; Myocardium; Natriuretic Peptide, Brain; Peptides; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors; Up-Regulation

In isolated cardiac myocytes, the direct effects of angiotensin II on cellular growth and gene expression were shown to be mediated by endothelin via the endothelin subtype A (ETA) receptor. To determine whether this pathway is also involved in the cardiovascular adaptations to a chronic activation of the renin-angiotensin system in vivo, the effects of a selective ETA receptor antagonist (LU 127043) were investigated in adult rats with renal artery stenosis. Four groups of rats (n=107) were studied over a period of 10 days after surgery: (1) sham-operated animals with saline administration, (2) rats subjected to left renal artery clipping with saline administration, (3) sham-operated rats with LU 127043 administration, and (4) rats subjected to left renal artery clipping with LU 127043 administration. LU 127043 (50 mg/kg) or saline was given by gavage twice daily starting 1 day before the operation. In clipped rats with saline administration, plasma renin activity, the ratio of left ventricular weight to body weight, and mRNAs for beta-myosin heavy chain and atrial natriuretic peptide were significantly elevated as early as 2 days after surgery. Blood pressure started to rise on the third postoperative day and attained a steady state hypertensive level by day 6. Blockade of ETA receptors had no effects on plasma renin activity or the time course of hypertension in clipped animals but completely prevented left ventricular hypertrophy and the re-expression of the beta-myosin heavy chain and atrial natriuretic peptide genes on day 2. While the expressions of the beta-myosin heavy chain and atrial natriuretic peptide genes were not different from saline-treated, clipped animals after day 4, the development of left ventricular hypertrophy remained markedly blunted (-50%) during ETA receptor blockade until day 10. These results show that a continuous blockade of ETA receptors significantly attenuates the development of left ventricular hypertrophy and, more transiently, fetal gene expression in the early phase of renovascular hypertension. Since neither blood pressure nor the increase in plasma renin activity was significantly altered by ETA receptor blockade, the inhibitory influences of the ETA receptor antagonist on left ventricular hypertrophy and gene expression were mediated most likely through a direct blockade of myocardial ETA receptors.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Endothelin Receptor Antagonists; Female; Heart Rate; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Myosin Heavy Chains; Phenylpropionates; Pyrimidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptors, Endothelin; Renin; RNA, Messenger

Hig levels of circulating atrial natriuretic factor (ANF) have been reported in several physiopathologic conditions like hypertension, heart and renal failure, pregnancy and high sodium intake. Nevertheless, neither relationships with water-sodium space regulation nor the role of an ANF vascular relaxant effect have been yet defined. The aim of present experiments was to characterize the contribution of circulating ANF and its vascular relaxing effects in the two kidney-two clip (2K2C) experimental model of renovascular hypertension. Complementary, plasma metabolites nitrite/nitrate of nitric oxide (NO) was examined because of mediation for both (NO an ANF) through cGMP. Three results showed (two-four weeks after surgery): indirect systolic blood pressure (mmHg), 186 +/- 4 in HT and 122 +/- 1 in SH (p < 0.001); a significant increase of plasma ANF (fmol/ml) in HT (n = 7, 1221 +/- 253) vs. SH (n = 9, 476 +/- 82; p < 0.02). Nitrate/nitrite plasma concentrations (mumol/l) were mpt different between SH and. The relaxant effect of ANF (10(-9), 10(-8) and 10(-7) M) on phenylephrine (3,5 x 10(-6) M) contracted rings from HT rats was smaller than SH rats (10(-8) M, p < 0.05). Contractions to phorbol 12, 13-dibutyrate (seven weeks after surgery) were significantly higher in rings from HT rats (p < 0.001). We conclude: 1) in addition to decreased granularity in atrial myocardiocytes, high circulating values of ANF here described suggest an increased turnover of the peptide in 2K2C hypertensive rats; 2) lower significant vascular relaxant effects in HT rats would indicate down regulation of ANF receptors in this model; the latter would derive from high plasma ANF concentration and, tentatively, because of greater activity of protein kinase C in the vascular wall; 39 similar values of plasma nitrite/nitrate in SH and HT rats would indicate a comparable NO circulating availability in both groups.

Topics: Animals; Aorta, Abdominal; Atrial Natriuretic Factor; Blood Pressure; Hypertension, Renovascular; Kidney; Male; Muscle, Smooth, Vascular; Nitrates; Nitric Oxide; Nitrites; Rats; Rats, Wistar

Xueling(p.o.) obviously reduces the aldosterone content of renal hypertension rats, but not affecting markedly the endothelin, atrial natriuretic factor, calcitonin gene-related peptide, thromboxane B2 and 6-keto-prostaglandin F1 alpha. The content reduction of aldosterone is one of the mechanisms to lower blood pressure.

Topics: 6-Ketoprostaglandin F1 alpha; Aldosterone; Animals; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Drugs, Chinese Herbal; Endothelins; Female; Hypertension, Renovascular; Male; Random Allocation; Rats; Rats, Wistar; Thromboxane B2

To evaluate the hypotensive and renal effects of atrial natriuretic peptide (ANP) in one-kidney, one clip Goldblatt hypertensive rats with and without renal arterial stenosis.. The one-kidney, one clip hypertensive rats were divided into four groups: untreated time control, ANP-infused, unclipped and unclipped plus ANP-infused. The changes in blood pressure, glomerular filtration rate and renal excretory function were determined during intravenous vehicle and ANP infusions while the renal arterial clip was in place or removed acutely. One-kidney normotensive rats infused with ANP were used for comparison.. In one-kidney control rats, ANP infusion at doses of 0.15, 0.30 and 0.45 microg/kg per min decreased the mean blood pressure from 121 +/- 4 to 108 +/- 5 (9%, P < 0.05), 104 +/- 5 (17%, P < 0.05) and 89 +/- 4 mmHg (25%, P < 0.05), respectively. There was no significant change in glomerular filtration rate. However, the absolute sodium excretion rate increased significantly, by 343 +/- 66, 770 +/- 91 and 786 +/- 78%, respectively. A comparable magnitude of increase in the fractional sodium excretion was noted. In one-kidney, one clip hypertensive rats, the similar three doses of ANP infusion reduced blood pressure from 179 +/- 7 to 162 +/- 8 (8%, P < 0.05), 146 +/- 9 (17%, P < 0.05) and 138 +/- 8 mmHg (22%, P < 0.05), respectively. A slight but insignificant increase in renal function was observed during ANP infusion. Removal of the renal arterial clip reduced blood pressure rapidly and caused a transient increase in renal function. Subsequent infusion of ANF further reduced blood pressure but increased sodium and water excretion markedly.. There is a blunted natriuresis and diuresis in response to ANP infusion in one-kidney, one clip hypertensive rats. Surgical removal of the clip from the renal artery restores the natriuretic and diuretic effects of ANP.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Glomerular Filtration Rate; Hypertension, Renovascular; Kidney; Male; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor

In our study we have examined the mRNA levels of nitric-oxide-(NO-)synthases in rat kidneys during states of stimulated and reduced renin gene expression, to find out whether renal mRNA levels of NO-synthases are correlated with the activity of the renin system. Stimulation of the renin system was achieved by unilateral renal artery clipping (2-kidney/1-clip rats), treatment with the angiotensin II (ANG II) antagonist losartan (40 mg/kg), application of furosemide (12 mg x kg-1 x day-1) and a low-sodium diet (0.02% w/w Na+), which increased renin mRNA levels to 464%, 495%, 309% and 219% of those of control animals, respectively. Inhibition of the renin system was achieved in the nonclipped (contralateral) kidneys of 2-kidney/1-clip rats and in the kidneys of rats which were fed a high-sodium diet (4% w/w Na+); in both cases renin mRNA levels decreased to about 50% of the control values. First screening of the gene expression of brain-type NO-synthase (b-NOS), endothelial NOS (e-NOS) and inducible NOS (i-NOS) during all these alterations of the renin system was done using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Results from such noncompetitive PCR experiments indicated that only b-NOS mRNA levels change concordantly with the levels of renin. These changes in b-NOS mRNA levels were checked by the more reliable method of RNase protection assay. Results of the RNase protection assay proved that the renal levels of b-NOS mRNA were significantly increased by about 50% after a low-sodium diet and hypoperfusion of the kidney. Given a stimulatory role of endothelium-derived relaxing factor (EDRF)/NO on the renin system our findings may provide the first evidence that increases of renal levels of b-NOS mRNA and, as a consequence, of renal EDRF/NO formation could be important mediators of the well-known effect of salt intake and hypoperfusion on the renin system.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Atrial Natriuretic Factor; Base Sequence; Brain; Hypertension, Renovascular; Kidney; Male; Molecular Sequence Data; Nitric Oxide Synthase; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Renal Artery; Renin; RNA, Messenger

We determined the renal and depressor activities of 10, 50, and 100 pmol/kg per minute i.v. of human atrial natriuretic peptide-(99-126) in conscious one-kidney, one clip dogs with chronic hypertension and modest renal dysfunction, as indicated by mild proteinuria. Atrial natriuretic peptide increased fractional sodium excretion by 0.009 +/- 0.002, 0.042 +/- 0.005, and 0.049 +/- 0.007, respectively; urinary excretion of atrial natriuretic peptide by -0.4 +/- 0.8, 3.3 +/- 1.4, and 15.8 +/- 7.4 fmol/min; and cGMP excretion by 0.65 +/- 0.06, 1.65 +/- 0.08, and 4.88 +/- 0.85 nmol/min in one-kidney shams. The changes in fractional sodium excretion were significantly attenuated in the hypertensive dogs (0.005 +/- 0.002, 0.018 +/- 0.003, and 0.022 +/- 0.004, respectively) despite exaggerated increases in atrial natriuretic peptide excretion (3.3 +/- 1.6, 22.0 +/- 5.0, and 46.6 +/- 10.8 fmol/min) and cGMP excretion (0.96 +/- 0.47, 4.51 +/- 1.27, and 7.06 +/- 1.38 nmol/min). The slope of the line relating urinary atrial natriuretic peptide to cGMP was significantly suppressed in the hypertensive dogs, suggesting a downregulation of the guanylate cyclase-linked receptors. The slope of the relationship between cGMP excretion and the natriuretic response was also depressed in the hypertensive dogs, indicating possible impairment of cGMP signal transduction. The differences between sham and hypertensive dogs were diminished when urinary levels of atrial natriuretic peptide were maximized by prior treatment with SQ 28603, an inhibitor of neutral endopeptidase EC 3.4.24.11. Atrial natriuretic peptide caused comparable decreases in mean arterial pressure and increases in glomerular filtration rate in sham and hypertensive dogs, suggesting similar vascular reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alanine; Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Diuretics; Dogs; Female; Humans; Hypertension, Renovascular; Injections, Intravenous; Kidney; Male; Neprilysin; Peptide Fragments

ANP-receptors affinities (KD) and capacities (Bmax) were assayed in cryosections of glomeruli from 'malignant' hypertensive rats (2K-1C) and spontaneously hypertensive rats (PHR). Plasma ANP concentration was twofold higher in 2K-1C (P < 0.05) and PHR (P < 0.02) than in the respective controls, KD and Bmax for rANP99-126 and ANP103-123 did not differ. ANP mediated cGAMP release in 2K-1C rats was also unaffected. ANP-C glomerular receptors (i.e. displacement of tracer binding with ANP103-123) were not down-regulated and had unchanged peptide binding affinity in either kidney of rats with 'malignant' hypertension and in PHR. The difference between Bmax for rANP99-126 and Bmax for rANP103-123 (ANP-A receptor binding) indicates moderate up-regulation of ANP-A receptors in the clipped, and down-regulation in the contralateral kidney of 2K-1C (2K-1C, right vs. left, P < 0.05). Since [ANP]pl, and also Bmax and KD for ANP were similar in both hypertension models investigated, changes of the [ANP]pl/ANP-receptor system can not completely explain the marked natriuresis of rats with 'malignant' hypertension.

Topics: Animals; Atrial Natriuretic Factor; Down-Regulation; Guanylate Cyclase; Hypertension; Hypertension, Malignant; Hypertension, Renovascular; Kidney Glomerulus; Kinetics; Male; Natriuresis; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor

Renal interstitial hydrostatic pressure (RIHP) plays a key role in the link between renal hemodynamics and the rate of the tubular reabsorption of sodium and water. Our objective was to determine whether the natriuretic response to a rise in RIHP induced by acute saline infusion would be altered in prehypertensive, Dahl salt-sensitive (DS) rats. We compared the effects of an acute saline load (2.5 ml/100 g BW over 30-min) on RIHP and urinary sodium excretion in Dahl salt-resistant (DR) (n = 11) and DS rats (n = 11) maintained from birth on a low-sodium diet. Baseline mean arterial pressure, glomerular filtration rate rate, and urinary sodium excretion did not differ between DR and prehypertensive DS rats. Urine flow rate and urinary sodium excretion increased significantly in both groups following saline loading. Increases were significantly (p < 0.05) less in the prehypertensive DS rats (0.32 +/- 0.07 to 3.62 +/- 0.79 microEq/min) than in the DR rats (0.71 +/- 0.22 to 6.30 +/- 1.35 microEq/min). RIHP also increased significantly in both groups, but did not differ significantly in DR (7.3 +/- 1.1 to 9.7 +/- 1.7 mmHg) vs. DS rate (7.9 +/- 1.0 to 9.8 +/- 1.3 mmHg). At an equal mean arterial pressure, DS rats showed a reduced natriuretic capacity after an acute saline load, prior to the development of hypertension. Renal tubular sensitivity to the increased RIHP that was induced by an acute saline load was blunted in prehypertensive DS rats.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Body Weight; Diet, Sodium-Restricted; Glomerular Filtration Rate; Hydrostatic Pressure; Hypertension, Renovascular; Male; Potassium; Rats; Rats, Sprague-Dawley; Salts; Sodium; Sodium, Dietary

1. Elevated peripheral atrial natriuretic peptide (ANP) levels were observed in 12 patients with unilateral renal artery stenosis (U-RAS). 2. Renal extraction of ANP was higher across the affected than the unaffected kidney in U-RAS, provided the glomerular filtration rate in the affected kidney was not severely reduced (> 12 mL/min). As ANP is a high clearance compound, reduced flow on the affected side may result in increased renal extraction of ANP. 3. When glomerular filtration rate (GFR) in the affected kidney was severely reduced (< 12 mL/min), renal extraction of ANP was also reduced, possibly contributing to increased circulating ANP levels in this subgroup. 4. Overall, renal extraction of ANP was inversely correlated to peripheral ANP levels in patients with U-RAS. This might be explained by progressive sodium retention as GFR falls leading to volume expansion and increased ANP secretion.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Hypertension, Renovascular; Kidney; Male; Middle Aged; Renal Artery Obstruction; Renin

The heart has an endocrine activity which depends on the secretion of a natriuretic, diuretic and hypotensive factor contained in osmophilic, secretory granules localized in the myocardiocytes and called "atrial specific granules" (the atrial natriuretic factor, ANF). In this paper, the relationship between these specific granules and renovascular hypertension elicited by the constriction of both renal arteries was investigated at the electron microscope level during the acute, subacute and chronic phases of hypertension. Male Wistar CHbb THOM rats were divided in three groups: 1) clipped rats; 2) sham operated rats; 3) ether anesthesia as unique manoeuver 48 h before decapitation. Blood pressure increased progressively after the constriction of both renal arteries. The atrial specific granules were not affected by ether anesthesia alone; 48-72 h after clipping the granules almost disappeared and this situation persisted up to the 6th week. In sham operated rats the picture was very similar to the clip rats 48 and 72 h after surgery (severe granule disappearance); in contrast, at one, two and six weeks after surgery, the granularity of cardiomyocytes in sham rats was absolutely restored. It is concluded that: 1) similarities in morphology of atrial specific granules in sham and clip rats 48 and 72 h after surgery would suggest that stress plays a primary role in determining the observed images; 2) thereafter, the contrast between sham and clip rats 1, 2 and 6 weeks after surgery would indicate that the ANF is linked to the subacute and chronic regulation of renovascular hypertension.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Constriction; Hypertension, Renovascular; Male; Rats; Rats, Wistar; Renal Artery

The present study was aimed to determine the effect of caffeine on the development of renal hypertension. Two-kidney, 1-clip (2K1C) hypertension and deoxycorticosterone acetate (DOCA, 200 mg/kg, subcutaneous implantation)-salt (0.9% NaCl drinking) hypertension were instituted in Sprague-Dawley rats. They were then grouped into two groups each: one was supplemented with caffeine (0.1%) in their drinking solution and the other was not. Systolic blood pressure was measured up to 24 days. Caffeine exacerbated the development of 2K1C hypertension in association with a higher plasma renin concentration (PRC). Caffeine ingestion, however, did not exacerbate but ameliorated DOCA-salt hypertension in which PRC was comparable between the caffeine-ingested and control groups. Concentrations of plasma atrial natriuretic peptide (pANP) were significantly different between the caffeine-ingested and control groups neither in 2K1C nor in DOCA-salt rats, suggesting that ANP was not responsible for the modified blood pressure. Acute caffeine infusion (350 micrograms/min, 30 min) in anesthetized normotensive rats caused increases in urinary excretion (volume and sodium) and in PRC without significantly affecting the blood pressure and pANP. These results suggest that caffeine specifically exacerbates 2K1C hypertension through increasing renin release whereas it ameliorates DOCA-salt hypertension possibly through increasing renal excretion.

Topics: Administration, Oral; Animals; Atrial Natriuretic Factor; Blood Pressure; Caffeine; Desoxycorticosterone; Hypertension, Renovascular; Infusions, Intravenous; Male; Rats; Rats, Sprague-Dawley; Renin

To investigate the regulation of papillary atrial natriuretic factor (ANF) receptors and the differential regulation of glomerular ANF receptor subtypes in one-kidney, one clip (1-K,1C) hypertension.. Plasma immunoreactive ANF levels and atrial and ventricular ANF content were measured in 1-K,1C rats and their normotensive uninephrectomized controls. Glomerular and papillary ANF receptor subtypes were characterized by competitive radioligand binding assay. Stimulation of cyclic GMP (cGMP) production, by increasing ANF doses, was examined in isolated glomeruli.. Plasma amino-terminal ANF levels were higher in 1-K,1C than in control rats. ANF concentrations in the left atrium were lower and ventricular ANF concentrations were higher in the 1-K,1C group. Competition binding curves for glomerular membranes revealed the presence of two binding sites (ANF-R1 and ANF-R2) in both groups. Total glomerular ANF receptor density was lower in 1-K,1C rats than in their normotensive controls. Both receptor subtypes were downregulated in 1-K,1C rats and their relative proportion was similar to that in glomerular preparations from the controls. ANF-stimulated cGMP production by isolated glomeruli was lower in 1-K,1C than in normotensive rats. In papillary membranes, ANF was bound to a homogeneous population of high-affinity binding sites in both groups. A modest augmentation in the density of papillary ANF receptors was observed in 1-K,1C rats.. Glomerular and papillary ANF receptors may be regulated differently in the presence of elevated plasma ANF levels. The present results indicate that the downregulation of glomerular ANF-R1 and the reduced cGMP response may lead to altered sodium and water handling by the kidney of 1-K,1C hypertensive rats.

Topics: Animals; Atrial Natriuretic Factor; Down-Regulation; Heart Atria; Heart Ventricles; Hypertension, Renovascular; Kidney; Kidney Glomerulus; Kidney Medulla; Male; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor

Previous studies have shown the effects of atrial natriuretic factor (ANF) on rats with renovascular hypertension (RVH). In the present study low dose alpha-hANF (0.025 microgram/kg/min) was administered intravenously for 60 minutes to seven RVH patients. Results demonstrated an inhibition of renin-angiotensin-aldosterone system (RAAS), reduction of plasma catecholamine and arginine vasopressin(AVP), diuresis and natriuresis, increase of hematocrit and creatinine clearance, and slight decrease of blood pressure. These results showed that most factors involved in the establishment and maintenance of RVH are affected by ANF infusion.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Female; Heart Rate; Humans; Hypertension, Renovascular; Male; Middle Aged; Renin-Angiotensin System

In 19 patients with unilateral renal artery stenosis and subsequent renovascular hypertension plasma renin activity (PRA), plasma concentrations of atrial natriuretic peptide (ANP), erythropoietin (Epo), H+ and HCO3-, as well as pO2 and pCO2 were assessed in renal venous blood of the 'ischaemic' and normally perfused kidney, both in arterial blood and in the inferior vena cava distally from the orifices of the renal veins. PRA and ANP were significantly elevated in venous blood of the ischaemic kidney as compared with the normally perfused kidney. In contrast to PRA and ANP, plasma concentrations of Epo were similar in blood withdrawn at all vascular sites. pO2 and pCO2, as well as blood H+ and HCO3- concentrations in venous blood of the ischaemic kidney were of the same magnitude as of the normally perfused kidney. From the results presented in this paper it follows that (i) in contrast to plasma renin activity and ANP, unilateral renal 'ischaemia' does not influence plasma concentrations of Epo in renal venous blood, and (ii) chronic haemodynamic alterations do not seem to influence Epo secretion by the kidneys.

Topics: Adult; Atrial Natriuretic Factor; Erythropoietin; Female; Humans; Hypertension, Renovascular; Male; Middle Aged; Oxygen; Renal Veins; Renin

1. This study investigated the effect of atrial natriuretic peptide on renin release from the kidney. The in vitro direct effect was examined in the animal experiment using renal cortical slices of rat, and the in vivo effect was observed in the human infusion study. 2. In the in vitro experiments, alpha-human atrial natriuretic peptide (alpha-hANP) ranging 10(-9) to 10(-6) mol/L did not change the basal renin release rate from the renal cortical slices (-9% at 10(-6) mol/L, NS). Isoproterenol (10(-6) mol/L) increased renin release by 40% (P < 0.001), whereas angiotensin II (10(-6) mol/L) suppressed it by 48% (P < 0.001). However, alpha-hANP did not affect the stimulative effect of isoproterenol or the inhibitory effect of angiotensin II. 3. Also in the human study, infusion of 25 ng/kg per min alpha-hANP failed to change the plasma renin activity in normotensive subjects (-4%) or patients with essential hypertension (+5%), or even in patients with raised renin levels such as renovascular hypertension (+10%) or congestive heart failure (-13%). 4. These results put forth negative views on the direct involvement of atrial natriuretic peptide in renin release from the juxtaglomerular apparatus.

Topics: Adult; Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Failure; Humans; Hypertension; Hypertension, Renovascular; In Vitro Techniques; Kidney Cortex; Middle Aged; Rats; Rats, Sprague-Dawley; Renin

To analyze the determinants of left ventricular (LV) performance (myocardial afterload, chamber size, mass, and contractility) in Goldblatt hypertension, 19 anesthetized one-kidney, one-clip (1K1C) and 28 two-kidney, one-clip (2K1C) male Wistar rats were studied 58 to 62 days after clipping, together with 19 sham-operated and 13 normal rats (controls), by M-mode echocardiography using necropsy-validated methods of measurement. The LV fractional shortening was inversely related to end-systolic stress in all groups (r = -0.89 to -0.95, all P less than .00001): 7 2K1C (25%) and 9 1K1C (47%) had fractional shortening above the upper confidence limit in control animals. Both 1K1C and 2K1C with high LV performance had severe hypertension, inadequate LV hypertrophy, with resultant high wall stress (both P less than .005), increased LV chamber dimension (P less than .005 and P less than .05, respectively) and high afterload-corrected fractional shortening (both P less than .001); 2K1C also had high plasma renin activity and atrial natriuretic factor levels (both P less than .01). Rats with normal LV performance exhibited mild hypertension, adequate LV hypertrophy (normalizing wall stress), and normal LV chamber size and afterload-corrected fractional shortening. Thus, 8 1/2 weeks after clipping, adequate LV hypertrophy allows maintenance of normal LV function by normalizing myocardial afterload in a majority of rats with Goldblatt hypertension, whereas increased LV contractility (and possibly use of preload reserve in 1K1C) maintains normal LV function in the presence of inadequate LV hypertrophy and elevated wall stress, in a substantial minority of rats that developed more severe Goldblatt hypertension.

Topics: Animals; Atrial Natriuretic Factor; Cardiomegaly; Echocardiography; Heart Ventricles; Hypertension, Renovascular; Myocardial Contraction; Rats; Renin; Ventricular Function, Left

Topics: Animals; Aorta, Thoracic; Atrial Natriuretic Factor; Cyclosporine; Endothelium, Vascular; Hypertension, Renovascular; Kidney; Male; Rats; Rats, Inbred Strains; Renin; Renin-Angiotensin System

The central atrial natriuretic peptides (ANF)-system was investigated in volume-dependent, one-kidney, one-clip (1K1C) and renin-dependent two-kidney, one-clip (2K1C) renovascular hypertensive rats by radioimmunological measurement of ANF concentration in 18 selected brain areas. Significant changes were found in nine brain areas of 1K1C and in eight brain areas of 2K1C hypertensive rats. Except undirectional changes in the organum vasculosum laminae terminalis and the supraoptic nucleus, ANF concentration was changed in the opposite direction in all other brain areas, with an activation of the central ANF system in 1K1C and an inhibition in 2K1C hypertension. The localization of the alterations (circumventricular organs, anteroventral third ventricle region, hypothalamo hypophyseal system, brain stem) implies major differences in the central regulation of blood pressure and electrolyte and fluid homeostasis between these two models. The activation of the central ANF system in 1K1C hypertension may be a compensatory mechanism to prevent further increments in blood pressure and plasma volume. In contrast, the depression of the central ANF system in 2K1C hypertension may promote the elevation of the blood pressure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Brain; Brain Chemistry; Hypertension, Renovascular; Male; Plasma Volume; Rats; Rats, Inbred Strains

Effects of high salt intake on the early onset of hypertension were examined in two-kidney, one-clip rats. They were divided into high salt and control groups which were supplied with 1.0% NaCl and tap water, respectively, as a drinking solution for 12 days after clipping the left renal artery. The high salt group showed a lower plasma renin concentration and a higher plasma atrial natriuretic peptide (ANP) along with an attenuation of the magnitude of early hypertension, as compared with the control group. A significant positive correlation between blood pressure and plasma renin concentration and an inverse correlation between plasma renin concentration and ANP were shown. Cortical renal renin content was comparable between the two groups. In another two groups of sham-clipped rats, the high salt group did not differ from the tap water-drinking group in any of the parameters examined, except that ANP was significantly higher. These results demonstrate that high salt intake attenuates the developmental phase of hypertension in two-kidney, one-clip rats by increasing the ANP and suppressing the release of renin.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Hypertension, Renovascular; Kidney; Male; Rats; Rats, Inbred Strains; Renin; Sodium Chloride; Sodium, Dietary

The extractions of atrial natriuretic factor (EANF) and the glomerular filtration marker 51Cr-ethylenediamine tetraacetic acid (EEDTA) were determined before and after intravenous injection of furosemide across each of the two kidneys during renal vein catheterization in hypertensive patients with unilateral or bilateral renovascular disease. Before administration of furosemide, EANF was approximately 55% across both the more and the less affected kidney while EEDTA was significantly decreased across the more affected kidney. Significant lateralization of renin secretion to the more affected kidney was found, demonstrating an enhanced ipsilateral formation of renin. Administration of furosemide caused a significant decrease in EEDTA across the less affected kidney while the ipsilateral EANF did not change. Furosemide caused no change in EEDTA or EANF across the more affected kidney. No significant correlations were found between EANF and EEDTA. These results demonstrate that the extraction of ANF is unchanged across the chronic ischemic human kidney. Furthermore, in the single kidney, changes in EEDTA, as induced by furosemide, are not related to changes in ipsilateral EANF. Since the relation between simultaneously determined single kidney extractions of ANF and 51Cr-EDTA reflects the relation between the single kidney clearance of ANF and the ipsilateral glomerular filtration rate, our data indicate a dissociation between changes in the single kidney glomerular filtration rate and the ipsilateral total renal clearance of ANF.

Topics: Atrial Natriuretic Factor; Chromium Radioisotopes; Edetic Acid; Female; Furosemide; Glomerular Filtration Rate; Humans; Hypertension, Renovascular; Ischemia; Kidney; Male; Middle Aged; Renin-Angiotensin System

We assessed the changes in atrial natriuretic peptide (ANP) and its messenger RNA (mRNA) levels in atria and ventricles in relation to hemodynamic factors during antihypertensive treatments in two-kidney, one-clip renovascular hypertensive rats (RHRs). Hypertension of 10-week duration caused a twofold increase in the left ventricular weight/body weight ratio, a significant increase in left ventricular end-diastolic pressure, and an eightfold increase in left ventricular ANP mRNA levels in RHRs, as compared with the levels in control rats. Uninephrectomy or 4 weeks of treatment with the converting enzyme inhibitor enalapril reduced the blood pressure to the control level, with the complete reversal of left ventricular hypertrophy, left ventricular end-diastolic pressure, and ANP mRNA levels. Four weeks of treatment with the arterial vasodilator hydralazine significantly, but not completely, reduced the high blood pressure, but it did not influence left ventricular hypertrophy, end-diastolic pressure, and ANP mRNA levels. The increased ANP synthesis observed in the right ventricles of RHRs also reverted to the control level by uninephrectomy or enalapril treatment, but not by hydralazine, with a time course similar to that of left ventricular ANP. In addition, uninephrectomy caused the left and right ventricular ANP and ANP mRNA levels of RHRs to fall to the levels of control rats as early as 1 week, despite persistent left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blotting, Northern; Cardiomegaly; Enalapril; Heart Ventricles; Hemodynamics; Hydralazine; Hypertension, Renovascular; Male; Nephrectomy; Rats; Rats, Inbred Strains; RNA, Messenger; Time Factors

The influence of sodium intake on the gene expression and circulating levels of atrial natriuretic factor (ANF) was investigated in unanesthetized rats with one-kidney, one-clip renal hypertension. After clipping, the rats were maintained for 3 weeks either on a salt-deficient (n = 11) or a regular-sodium diet (n = 10). Animals which had received the regular-sodium diet exhibited significantly higher ANF mRNA levels in their right and left atria than salt-restricted animals, whereas there was no significant difference in plasma ANF levels.

Topics: Animals; Atrial Natriuretic Factor; Diet, Sodium-Restricted; Gene Expression; Heart Atria; Hypertension, Renovascular; Male; Rats; Rats, Inbred Strains; RNA, Messenger; Sodium; Water-Electrolyte Balance

The atrial natriuretic factor (ANF) is a hormone whose effects and mode of secretion have been determined. But its exact role in the regulation of volemia in comparison with that of the renin-angiotensin system is still to be defined. Studies of human diseases associated with an increase of ANF plasma concentration may help reach this goal. The mechanisms resulting in elevated ANF plasma concentrations (increase of secretion, decrease of catabolism of the hormone) and the effects of these high levels of ANF on renal functions and circulation are analysed in chronic cardiac failure, mitral stenosis, pulmonary artery hypertension, acute tachycardias, chronic and acute renal failures and in the course of cardiac transplantation. The therapeutic usefulness of drugs inhibiting ANF catabolism (blockers of the clearance receptors for ANF and inhibitors of the enzymes degrading ANF) is also considered.

Topics: Acute Kidney Injury; Atrial Natriuretic Factor; Heart Failure; Heart Transplantation; Humans; Hypertension, Pulmonary; Hypertension, Renovascular; Kidney Failure, Chronic; Mitral Valve Stenosis; Tachycardia, Supraventricular

The renal actions of atriopeptin III were compared in sham control, spontaneous and Goldblatt (2-K 1-C) hypertensive rats. Atriopeptin III, administered at 125. 250 and 500 ng/kg or 1.0, 1.5 and 2.0 micrograms/kg, into sham control rats had no effect on blood pressure or renal haemodynamics but caused dose related increases in urine flow, absolute and fractional sodium excretions, from 44 to 248%. Similar excretory responses to this dose range of atriopeptin III were obtained in spontaneously hypertensive rats. Atriopeptin III given at 125, 250 and 500 ng/kg into 2-K 1-C Goldblatt hypertensive rats increased reversibly left kidney urine flow, absolute and fractional sodium excretion by between 55 and 74% which were similar responses to those of sham control left kidneys. By contrast, atriopeptin III had much smaller effects on water and sodium excretions of the right clipped kidneys. These results suggest that atrial natriuretic peptides may be useful in mobilising fluid in genetic hypertension but their usefulness may be restricted in renovascular forms of hypertension.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Glomerular Filtration Rate; Hypertension; Hypertension, Renovascular; Kidney; Male; Peptide Fragments; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Renal Circulation; Sodium

We have previously found that chronic infusion of atrial natriuretic peptide (ANP) decreased mean arterial pressure (MAP) by 16% in two-kidney, one-clip (2K-1C) hypertensive rats, and we hypothesized that natriuresis might be modified through the pressure-natriuresis mechanism. We therefore decided to evaluate sodium balance in 2K-1C rats infused with ANP (0.5 micrograms/h for 4 days). The ANP infusion to the 2K-1C rats induced a significant decrease in MAP from 171 +/- 3 to a minimum value of 147 +/- 6 mm Hg after 2 days of treatment (p less than 0.001). Sodium excretion fell from 2,536 +/- 60 to 2,047 +/- 86 (p less than 0.001) and 2,211 +/- 96 mu Eq/24 h (p less than 0.05) by days 1 and 2 of ANP administration. Furthermore, fractional excretion of sodium intake decreased from 99.1 +/- 1.5 to 81.1 +/- 2.9 (p less than 0.001), 84.1 +/- 2.6 (p less than 0.05) and 85.9 +/- 5.15% (p less than 0.05) by days 1, 2 and 3 of ANP infusion, respectively, returning to basal values thereafter. The administration of vehicle (0.9% NaCl) did not induce any significant change in 2K-1C hypertensive rats. The infusion of either vehicle or the same dose of ANP to normotensive rats (0.5 micrograms/h, for 4 days) did not modify sodium balance throughout the experiment. These results strongly suggest that the ANP-induced decrease in MAP might be responsible for the transitory sodium retention observed in 2K-1C hypertensive rats during the administration of the peptide.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Hypertension, Renovascular; Male; Natriuresis; Rats; Rats, Inbred Strains; Sodium; Urine

Bilateral renal clearance experiments were performed to examine the effects of synthetic rat atrial natriuretic peptide (ANP, atriopeptin II) on the arterial blood pressure (BP) and individual kidney function in anesthetized 2-kidney, 1 clip Goldblatt hypertensive rats (n = 14) and normotensive rats (n = 15). Bolus administration of graded doses of ANP from 2.5 to 10 micrograms/kg produced dose-related reductions in BP in hypertensive and normotensive rats. Despite profound reductions in BP, there were significant increases in glomerular filtration rate, urine flow, absolute and fractional excretion rates of sodium and potassium, osmolar clearance, and free water clearance in the nonclipped kidney, whereas no significant changes in these renal indices occurred in the clipped kidney. The enhanced renal responses were dose-dependent. The normal kidney responded to ANP with similar magnitude. When ANP was infused intravenously (0.3 microgram/kg.min i.v.) during 2 h, BP maximally reduced by 36 +/- 2 mm Hg (24 +/- 1%) in the hypertensive group and by 27 +/- 2 mm Hg (22 +/- 2%) in the control group. Again, there were distinct renal responses between the two kidneys of hypertensive rats. These results indicate that ANP effectively reduces BP and preferentially increases the excretory function of the nonclipped kidney without compromising the function of the clipped kidney in this hypertensive model.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Diuresis; Glomerular Filtration Rate; Hypertension, Renovascular; Kidney; Male; Rats; Rats, Inbred Strains

The purpose of this study was to evaluate the hemodynamic effects induced by an infusion of synthetic rat atrial natriuretic peptide (rANP, 0.5 micrograms/h iv) during 5 consecutive days in conscious normotensive and two-kidney, one-clip hypertensive (2K,1C) rats. Changes in plasma ANP (pANP) levels and plasma renin activity (PRA) were also determined. The administration of ANP in 2K,1C rats induced a significant decrease in mean arterial pressure (MAP) from 169 +/- 3 to 138 +/- 3, and 149 +/- 3 mmHg by 2 and 5 days of infusion, respectively. This hypotension was accompanied by a significant fall in cardiac index (CI) from 400 +/- 16 to 348 +/- 14 ml.min-1.kg-1 after 2 days of ANP treatment. However, CI returned to the basal levels at the third day, and a significant decrease in total peripheral resistance (TPR) was observed by 3 and 5 days of ANP infusion. The administration of the same dose of ANP in normotensive rats did not induce changes in MAP, but CI decreased (P less than 0.001) transitorily during the first 2 days and returned to control values thereafter. Basal pANP levels were significantly elevated in the hypertensive animals (176 +/- 40 pg/ml) when compared with the normotensive rats (82 +/- 10 pg/ml). The ANP infusion resulted in lower (P less than 0.05) pANP levels in hypertensive (1,017 +/- 234 pg/ml) than in normotensive rats (3,466 +/- 975 pg/ml). PRA did not change in any group during the administration of ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Hemodynamics; Hypertension, Renovascular; Infusions, Intravenous; Male; Rats; Rats, Inbred Strains; Time Factors

In the present study, we have evaluated whether the hemodynamic effects of atrial natriuretic peptide (ANP) infusion in two-kidney, one-clip (2K, 1C) hypertensive rats are mediated by inhibition of the renin-angiotensin system (RAS). Hemodynamic determinations were performed by thermodilution in conscious, chronically instrumented animals. ANP (1.5 micrograms.kg-1.min-1) and converting-enzyme (CE) inhibitor captopril (1 mg/kg plus 1 mg.kg-1.h-1), produced a similar fall of blood pressure through different hemodynamic mechanisms. ANP induced hypotension by decreasing cardiac index (CI; from 337.3 +/- 24.9 to 255.1 +/- 21.3 ml.min-1.kg-1, P less than 0.001), whereas a fall in total peripheral resistance (TPR) was observed during CE inhibition (from 0.568 +/- 0.02 to 0.488 +/- 0.02 mmHg.min.ml-1.kg, P less than 0.05). In addition, the ANP-induced decrease in CI was not significantly modified by previous CE inhibition. Furthermore, the decrease in TPR induced by CE inhibition did not change when CE inhibitor was administered during ANP treatment. The results of the present study indicate that the acute hemodynamic responses to ANP in 2K, 1C hypertensive rats are not mediated through antagonism of the vasoconstrictor actions of the RAS.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Captopril; Heart Rate; Hemodynamics; Hypertension, Renovascular; Male; Rats; Rats, Inbred Strains; Reference Values; Renin; Vascular Resistance

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Glomerular Filtration Rate; Hypertension, Renovascular; Potassium; Rats; Rats, Inbred Strains; Sodium; Time Factors

The peptides angiotensin II (ANGII) and atrial natriuretic factor (ANF) regulate blood pressure and salt and water balance by producing antagonistic physiological effects in a variety of tissues. We used in vitro autoradiography with [125I] ANGII and [125I]ANF to compare receptor regulation for both peptides in various tissues in three experimental models of hypertension [two-kidney, one-clip (2K-1C); one-kidney, one-clip (1K-1C); desoxycorticosterone-salt (DOCA-SALT)] and three nonhypertensive control groups [two-kidney (2K-CON); one-kidney (1K-CON); salt-loaded (SALT-CON)]. Blood pressures at death were significantly higher in all three hypertensive groups compared to those in normotensive controls, but there were no significant differences among the hypertensive or normotensive groups, respectively. PRA was highest in the 2K-1C group and lowest in the DOCA-SALT and SALT-CON groups, but plasma ANF levels did not differ significantly among the hypertensive or normotensive groups. In the aorta, ANGII receptor binding was decreased in 2K-1C rats and increased in DOCA-SALT and SALT-CON rats; ANF receptor binding was moderately increased in all three hypertensive groups. Adrenal zona glomerulosa binding for ANGII was highest in the 2K-1C group and lowest in DOCA-SALT rats, while ANF binding was decreased in DOCA-SALT and SALT-CON animals. ANGII renal glomerular binding was increased in DOCA-SALT and SALT-CON groups, and ANF glomerular binding was decreased in the same two groups. In the brain, the subfornical organ showed increased binding for both ANGII and ANF in DOCA-SALT rats. Our results show that tissue receptor binding of ANGII and ANF is regulated in distinct patterns in different models of hypertension, and that these patterns are tissue specific and more complex than simple reciprocal regulation.

Topics: Adrenal Glands; Angiotensin II; Animals; Aorta; Atrial Natriuretic Factor; Brain; Brain Stem; Disease Models, Animal; Hypertension; Hypertension, Renovascular; Kidney Glomerulus; Male; Muscle, Smooth, Vascular; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Reference Values; Renin

One-kidney, one clip (1K1C) hypertension is often associated with an expanded plasma volume and (once the arterial clip is removed) with natriuresis. Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit, and renal glomerular ANF receptors were therefore studied in 1K1C rats and in their normotensive uninephrectomized controls before and after unclipping. Six hours after removal of the clip, BP was normal in the 1K1C group and plasma ANF presented a sharp decline but was still significantly higher than in the normotensive controls, with a slight difference being evident 24 hours after unclipping. Hematocrit was lower in the 1K1C rats than in their control counterparts, but this difference tended to disappear once the clip was removed, indicating a contraction of plasma volume in these unclipped 1K1C animals. The renal glomerular ANF receptor population was markedly smaller in 1K1C rats than in the uninephrectomized controls but showed a twofold increase in number and affinity 24 hours after unclipping. It is concluded that the up-regulation and enhanced affinity of glomerular ANF receptors (probably secondary to the decrease in plasma levels of ANF) may contribute to the natriuresis reported in hypertensive 1K1C animals on removal of the arterial clip.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Hypertension, Renovascular; Kidney Glomerulus; Male; Natriuresis; Rats; Rats, Inbred Strains; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Time Factors

We have investigated whether there is a relation between renin dependency of two-kidney, one-clip (2K1C) hypertensive rats and the density of renal glomerular and vascular atrial natriuretic factor (ANF) receptors. Conscious 2K1C rats with blood pressure of 150 mm Hg or higher were classified according to their sensitivity to the blood pressure-lowering effect of the angiotensin II antagonist saralasin. Both hypertension groups had lower body weights and greater relative heart weights than normotensive controls. Hematocrit was lower and plasma volume higher in saralasin-resistant animals than in either saralasin-sensitive or control rats. Plasma renin activity was higher in the saralasin-sensitive group than in the resistant rats. Plasma ANF concentration was greater in saralasin-resistant than in either normotensive or saralasin-sensitive animals. ANF was reduced in both atria of saralasin-resistant 2K1C animals but only in the left atrium of the sensitive group. Both hypertensive groups showed an increased ventricular ANF concentration. The number of glomerular ANF binding sites was significantly lower in the clipped kidney of both hypertensive groups. This lower density of binding sites was accompanied by an increased affinity. In saralasin-sensitive rats, the density of glomerular ANF receptors in the nonclipped kidney was significantly higher than in the controls. Saralasin-resistant rats exhibited a decreased number of vascular ANF binding sites in both mesenteric arteries and aorta. We conclude that through modulation of its glomerular and vascular receptors, ANF may contribute to the differential sodium handling of saralasin-sensitive and -resistant 2K1C hypertensive rats and to the reduced vascular responsiveness to ANF observed in the saralasin-resistant hypertensive rats.

Topics: Animals; Aorta, Thoracic; Atrial Natriuretic Factor; Binding Sites; Drug Resistance; Hypertension, Renovascular; Kidney Glomerulus; Male; Mesenteric Arteries; Rats; Rats, Inbred Strains; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Saralasin

Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit and renal glomerular ANF receptors were studied during the development of hypertension in two-kidney, one clip (2-K, 1C) rats and were compared with normotensive controls. Plasma ANF was elevated in the 2-K, 1C group in all stages of hypertension, even after 3 weeks when BP, although higher than in sham-operated animals, had not yet reached arbitrarily-set hypertensive levels. At this time, hematocrit was higher in the hypertensive rats than in the controls, but the difference later disappeared. Lower atrial ANF concentrations were observed in the 2-K, 1C group at week 3, but only in the right atrium. No difference in ANF levels was noted in either the left or right atrium between hypertensive and normotensive animals 5 and 7 weeks after clipping. The glomerular ANF receptor population was markedly smaller in the clipped left kidney of 2-K, 1C rats during all stages of hypertension, and in the untouched right kidney at 5 and 7 weeks after surgery, but was larger in the non-clipped right kidney in the pre-hypertensive phase (3 weeks). It is concluded that receptor density changes during the evolution of high BP in the 2-K, 1C Goldblatt model of experimental hypertension. Our data suggest that the increases and decreases in density of renal glomerular ANF receptors may play a role in the differential handling of sodium by the clipped and non-clipped kidney during the various stages of development of 2-K, 1C hypertension in the rat.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Hematocrit; Hypertension, Renovascular; Kidney Glomerulus; Male; Rats; Rats, Inbred Strains; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

To investigate the involvement of atrial natriuretic peptide (ANP) in secondary hypertension, we examined hormonal and renal responses to ANP infusion (0.025 microgram/kg/min) in 27 patients with renal parenchymal hypertension, 10 with primary aldosteronism, 8 with renovascular hypertension, and 15 normotensive subjects. The preinfusion plasma concentration of ANP was significantly higher in patients with renal parenchymal hypertension (120 pg/ml, p less than 0.01) and in patients with primary aldosteronism (98 pg/ml, p less than 0.05) than in the normotensive subjects (40 pg/ml), but it was not greater than in the patients with renovascular hypertension (73 pg/ml, NS). In the patients with renal parenchymal hypertension, plasma ANP correlated negatively with creatinine clearance (r = -0.76, p less than 0.001). Mean blood pressure (-5%, p less than 0.01) and plasma aldosterone (-40%, p less than 0.001) decreased to a similar degree in the four groups during ANP infusion. However, an increase in urinary sodium excretion caused by ANP was higher in the hypertensive than in the normotensive patients (+250% vs. +70%, p less than 0.01) and correlated positively with mean blood pressure during ANP infusion (r = 0.47, p less than 0.001). The removal of adenomas in the patients with primary aldosteronism significantly lowered both plasma levels of ANP and cyclic guanosine 2',3'-monophosphate and reduced an increase in sodium excretion during ANP infusion, whereas the responses of blood pressure and plasma aldosterone to ANP infusion were not altered by the operation. Thus, these results suggest that elevated ANP secretion and increased natriuretic responses to ANP may modify the blood pressure and body fluid volume status in some types of secondary hypertension.

Topics: Adrenal Gland Neoplasms; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Hormones; Humans; Hyperaldosteronism; Hypertension, Renal; Hypertension, Renovascular; Kidney; Osmolar Concentration; Postoperative Period; Reference Values; Renin

The influence of a 6-week treatment of female Wistar rats with one-kidney, one clip (1-K, 1 C) renal hypertension, with the calcium antagonist nifedipine on plasma volume, red cell Na+ handling and plasma atrial natriuretic peptide immunoreactivity (ANP-IR) was studied. Measurements were performed at 2 and 6 weeks after surgery. In 1-K, 1 C rats plasma volume was increased and red cell Na+ pump activity was reduced only after 2 weeks. Blood pressure, heart weights and plasma ANP were massively increased after both 2 and 6 weeks. 1-K, 1 C-rats treated with nifedipine had normal plasma volume, plasma ANP, and red cell Na+ pump activity in comparison with sham-operated rats. Increases in blood pressure and heart weights were attenuated. It is concluded that 1-K, 1 C hypertension in the rat is associated with cardiomegaly, rise in plasma ANP, initial hypervolemia and depression of the membrane Na+ pump. Nifedipine prevents the occurrence of hypervolemia and secondary phenomena such as rises in plasma ANP and cardiomegaly. This may play an important contributory role in the prevention of pathological sequelae.

Topics: Animals; Atrial Natriuretic Factor; Erythrocytes; Female; Hypertension, Renovascular; Nifedipine; Plasma Volume; Rats; Rats, Inbred Strains; Sodium Channels

1. The effects of atrial natriuretic polypeptide (ANP) on renal function were examined in renal wrap hypertensive rabbits and sham operated rabbits. 2. ANP (2 micrograms/min) induced hypotension, but did not produce significant diuresis, natriuresis or change in the glomerular filtration rate (GFR) in renal wrap hypertensive rabbits (n = 8). 3. In sham operated normotensive rabbits (n = 4), ANP induced significant diuresis (230%) and increased GFR by about 40%. 4. Thus, ANP was markedly less effective in the impaired kidneys of renal wrapped rabbits than in normal kidneys.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Diuresis; Glomerular Filtration Rate; Hypertension, Renovascular; Kidney; Male; Natriuresis; Rabbits

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Hypertension, Renovascular; Male; Rats; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

Conscious two-kidney, one clip rats with 150 mm Hg or higher systolic blood pressure were infused with saralasin for 60 minutes. Those with a blood pressure decline of 30 mm Hg or more were classified as saralasin-sensitive; those with a decrease of 10 mm Hg or less were considered saralasin-resistant. The animals were then housed in metabolic cages. Groups of sham-operated normotensive, saralasin-sensitive or saralasin-resistant two-kidney, one clip (2K1C) rats were infused with atrial natriuretic factor (Arg 101-Tyr 126), 100 ng/hr per rat, for 6 days. Corresponding control groups were sham-infused. Blood pressure was initially higher in the saralasin-sensitive groups (176 +/- 6 and 181 +/- 1 mm Hg, respectively) than in the saralasin-resistant groups (160 +/- 4 and 169 +/- 4 mm Hg, respectively). Atrial natriuretic factor infusion produced a gradual decline in blood pressure to 128 +/- 5 mm Hg, but only in saralasin-sensitive 2K1C animals. Urinary volume, initially higher in saralasin-sensitive hypertensive than in normotensive rats, was depressed during atrial natriuretic factor infusion. Urinary sodium excretion and water intake showed the same tendency, but the changes were not significant. No such modifications were observed in saralasin-resistant or sham-operated rats infused with atrial natriuretic factor. Body weight, which was higher in normotensive animals, was unchanged during atrial natriuretic factor infusion. Saralasin-sensitive, noninfused 2K1C rats were the only group with higher plasma renin activity than sham-operated, normotensive controls. Plasma aldosterone was higher in the former than in the other five groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Hypertension, Renovascular; Male; Rats; Rats, Inbred Strains; Renin; Renin-Angiotensin System; Saralasin

Atrial natriuretic factor (ANF) was studied in rat plasma and atria 1, 2, 4, 6, and 8 weeks after constriction of the left renal artery and removal of the contralateral kidney. Plasma ANF was elevated at all periods of investigation. A positive correlation was observed between plasma ANF and blood pressure (r = 0.56, p less than 0.001). The total atrial ANF content (microgram/atrium) in one-kidney, one clip (1K1C) rats was lower during Weeks 1 and 2, but only in the left atrium. Lower ANF concentrations (microgram/mg protein) were also evident in the left atrium at Weeks 1, 2, and 8, and in the right atrium at Week 8. A negative correlation between ANF in plasma and in the left atrium was discerned (r = 0.43, p less than 0.01). Blood pressure (184 +/- 4 vs 114 +/- 4 mm Hg), body weight, and plasma ANF were also examined in 1K1C rats and their normotensive controls before and after unclipping. Blood pressure was normalized 6 hours after unclipping. Plasma ANF declined in 1K1C rats within 6 hours after clip removal, but it was still higher than in the controls. Plasma ANF was similar in both groups on Days 9 and 13 after unclipping. There were no differences in atrial ANF between hypertensive and normotensive animals 13 days after unclipping. The high levels of plasma ANF observed in 1K1C rats probably are secondary to increased intra-atrial pressure caused by the dual mechanism of expanded plasma volume and high blood pressure.

Topics: Animals; Atrial Natriuretic Factor; Heart Atria; Hypertension, Renovascular; Male; Rats

Plasma atrial natriuretic factor concentrations were measured in 44 patients with mild untreated essential hypertension and 48 normotensive controls. Mean venous plasma atrial natriuretic factor concentrations were 13.2 (SEM 1.5) and 13.0 (1.3) ng/l in the hypertensive patients and controls, respectively. Plasma atrial natriuretic factor concentrations were significantly correlated with age in both groups. Plasma atrial natriuretic factor concentrations were also measured during renal vein catheterisation in a group of 15 hypertensive patients; of these, eight had renovascular hypertension, and in all eight cases plasma atrial natriuretic factor concentrations were increased in the aorta and inferior vena cava. It is concluded that mild essential hypertension is not associated with increased plasma atrial natriuretic factor concentrations, whereas an age related increase in concentrations occurs in hypertensive and normotensive people.

Topics: Adult; Age Factors; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Rate; Humans; Hypertension; Hypertension, Renovascular; Male; Middle Aged; Renal Artery Obstruction; Renin-Angiotensin System

We have measured the basal circulating level of atrial natriuretic factor (ANF) in hypertensive patients. Plasma ANF concentrations in 101 patients with mild untreated, essential hypertension and in 64 normotensive controls were 14.9 +/- 11.1 vs 11.9 +/- 7.7 pg/ml, p = NS respectively. Plasma ANF levels in the patients were correlated with mean arterial pressure (r = 0.35, p less than 0.001) and age (r = 0.38, p less than 0.001). Sixteen patients with uncontrolled hypertension despite treatment, had significantly higher plasma ANF levels (33.5 +/- 27.3 pg/ml, p less than 0.001). Forty other patients with hypertension were subjected to an abdominal aortography and a renal vein catheterism, in order to rule out renovascular hypertension. Of these subjects, 16 were without significant renal artery stenosis, 12 had left renovascular hypertension and 12 others right renovascular hypertension. Plasma ANF levels were maximal in the aorta and there were no differences between the ANF levels in the renal veins, whether the stenosis was on the right or left side. In conclusion, plasma ANF levels were not elevated in 101 untreated patients with mild essential hypertension. Together with the evidence of elevated intra atrial pressure in mild essential hypertension, as found by others, this suggests that ANF secretion might be impaired in this disease.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Humans; Hypertension; Hypertension, Renovascular; Male; Middle Aged

The temporal changes in the plasma concentration of immunoreactive atrial natriuretic factor (ANF) were studied in dogs (n = 5) before and after renal artery constriction to produce one-kidney, one-clip renovascular hypertension. Three days after renal artery constriction, circulating ANF increased from 34 +/- 7 to 344 +/- 129 pg/ml (P less than 0.05) in association with a 38-mmHg elevation of mean arterial pressure and increases in plasma renin and aldosterone levels. Plasma renin and aldosterone remained elevated for 9 days after renal artery constriction. Arterial pressure stabilized at this elevated level of 35-40 mmHg above base line for the duration of the 4 wk after renal artery constriction. Right atrial filling pressure did not change significantly (P greater than 0.05) after constriction of the renal artery. This observation suggests that volume expansion with right atrial distention is not the only stimulus for release of ANF in these hypertensive dogs. Plasma ANF remained significantly elevated above base-line levels for 7 days postconstriction even though a twofold decrease from the maximal response of 344 +/- 129 pg/ml on day 3 to 168 +/- 48 pg/ml on day 7 was observed during this same time interval. Plasma ANF continued to decrease toward prehypertensive levels throughout the remainder of the established phase of the hypertension lasting an additional 21 days of observation. The mechanisms for this observed pattern of plasma ANF are unclear but may involve changes in left atrial distention and stretch as a stimulus for hormone secretion with progression of the hypertension.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Dogs; Female; Hemodynamics; Hypertension, Renovascular; Natriuresis; Renin; Time Factors

The plasma levels of immunoreactive (IR)-ANF have been evaluated by radioimmunoassay in several models of experimental hypertension and in human hypertension. In all models of experimental hypertension so far studied, the plasma levels of IR-ANF are consistently increased. This is accompanied by a decrease, at certain time intervals, of the IR-ANF levels in the left atrium. In human essential hypertension, the plasma levels of IR-ANF are not increased except in the severe form (diastolic blood pressure above 110 mmHg). In renovascular hypertension, the peripheral levels of IR-ANF are not different from the normal levels but are increased above normal in aortic blood.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Hypertension; Hypertension, Renovascular; Male; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Saralasin; Sympathetic Nervous System

The one-kidney, one-clip model of rat hypertension was found to have an increased natriuresis following chronic infusion of atrial natriuretic factor (ANF). We have now found that this natriuretic effect of ANF is associated with a suppression of the initially elevated urinary excretion of norepinephrine and epinephrine and increase of the excretion of the main dopamine metabolite-dihydroxyphenylacetic acid as well as of the urinary dopamine to norepinephrine ratio. These data are compatible with the hypothesis that ANF suppresses the increased sympathetic activity in this model of hypertension and this action combined with opposite changes of dopamine may contribute to the natriuretic effect of ANF.

Topics: Animals; Atrial Natriuretic Factor; Creatinine; Diuresis; Dopamine; Hypertension, Renovascular; Male; Natriuresis; Norepinephrine; Rats; Rats, Inbred Strains; Sympathetic Nervous System

The studies described in this report emphasize the potential importance of atrial natriuretic factor in affecting systemic and renal hemodynamics, sodium excretion and components of the renin-angiotensin-aldosterone system. It should be emphasized, however, that at present there is no direct and unequivocal evidence that ANF is secreted into the blood. Until this is done and until the factors that regulate its secretion have been established, its potential physiological role must remain speculative.

Topics: Adrenal Glands; Aldosterone; Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Diuresis; Dogs; Drug Evaluation, Preclinical; Hemodynamics; Hypertension, Renovascular; In Vitro Techniques; Kidney; Natriuresis; Rats; Renal Circulation; Renin-Angiotensin System; Structure-Activity Relationship; Vasoconstriction; Vasodilation

Hemodynamic responses to synthetic atrial natriuretic factor (ANF), were studied in renin-dependent two-kidney, one-clip (2K,1C) and deoxycorticosterone (DOC) salt-treated hypertensive rats as well as normotensive controls. ANF infusion (800 pmol/kg prime, 120 pmol X kg-1 X min-1 for 60 min) decreased blood pressure (BP) more in conscious 2K,1C (-24 +/- 4%) than in DOC salt-treated (-12 +/- 4%, P less than 0.05) or control rats. Hemodynamic parameters were also evaluated during graded infusion of three doses, each for 30 min. At 24 and 120 pmol X kg-1 X min-1, ANF lowered BP in 2K,1C rats, both conscious (from 156 +/- 6 to 144 +/- 7, P less than 0.05 and 135 +/- 5 mmHg, P less than 0.05) and anesthetized (from 148 +/- 7 to 138 +/- 7, P less than 0.05 and 128 +/- 7, P less than 0.05). In anesthetized 2K,1C, BP changes were associated with reduction in total peripheral resistance (TPR) that became significant at 120 pmol X kg-1 X min-1 (-10 +/- 2%), whereas cardiac output (CO) and stroke volume (SV) were unchanged. In DOC-salt-treated rats these doses did not lower BP despite progressive falls in CO (-7 +/- 3% and -24 +/- 5%, P less than 0.05) and SV (-8 +/- 2% and -23 +/- 5%, P less than 0.05), which were balanced by a simultaneous rise in TPR (+12 +/- 4% and +26 +/- 10%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Constriction; Desoxycorticosterone; Dose-Response Relationship, Drug; Hemodynamics; Hypertension; Hypertension, Renovascular; Kidney; Male; Rats; Rats, Inbred Strains; Sodium Chloride

Chronic infusion of atrial natriuretic factor (ANF) decreased blood pressure in two-kidney, one clip (2-K, 1C), spontaneously hypertensive rat (SHR) and one-kidney, one clip (1-K, 1C) models of experimental hypertension in the rat, but produced increased sodium excretion only in the 1-K, 1C model. In ANF-infused 2-K, 1C animals plasma renin activity did not differ from normotensive controls. Atrial content of immunoreactive (ir) ANF was significantly lower in SHR and 1-K, 1C animals. At 40-50 days old, cardiomyopathic hamsters had a higher concentration of plasma irANF and a lower ANF content in the left but not in the right atrium, although the difference in plasma ANF was more obvious once heart failure was well established. At 110-130 and 200-300 days old, the hamster atrial ANF content was not only lower in the left but also in the right atrium. No differences were observed in plasma irANF between normal subjects and either untreated or treated essential hypertensive patients. However, a significantly higher plasma ANF was observed in two groups with secondary hypertension, primary hyperaldosteronism and renovascular hypertension. Bolus injection of ANF into healthy subjects produced a dose-related decrease in blood pressure and an increase in the heart rate and natriuresis.

Topics: Adult; Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathies; Cricetinae; Humans; Hypertension; Hypertension, Renovascular; Male; Mesocricetus; Natriuresis; Peptide Fragments; Rats; Rats, Inbred Strains; Rats, Inbred WKY; Renin

The intravenous injection of an ED50 natriuretic dose (1 microgram) of synthetic ANF decreases blood pressure by 61 +/- 6 mmHg in 2-K, 1-C, and of 45 +/- 6 mmHg in 1-K, 1-C hypertensive rats, which was positively correlated with its initial level only in the 2-K, 1-C group. The hypotensive response lasted longer in the latter (greater than 40 min) than in normotensive sham-operated rats. No difference in duration was seen between 1-K, 1-C hypertensive and its uninephrectomized normotensive controls. The diuretic response to ANF was higher in 2-K, 1-C rats. No hematocrit changes were observed in any group. ANF induced a rise in urinary kallikrein in all groups but the 1-K, 1-C. Urinary kallikrein excretion was positively correlated with natriuresis in normotensive but not in hypertensive groups. ANF induced an increase in urinary cGMP excretion in all groups but the 1-K, 1-C, and an increase in plasma cGMP in the normotensive sham-operated animals. Our results suggest that the fall in blood pressure induced by synthetic ANF could be due to vasodilatation, a drop in cardiac output cannot, however, be eliminated. Whether the hypotensive effect of ANF is mediated by cGMP remains to be demonstrated.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Disease Models, Animal; Female; Hypertension, Renovascular; Hypotension; Kallikreins; Nephrectomy; Rats; Rats, Inbred Strains; Time Factors

A 24-amino acid residue synthetic atrial natriuretic factor (ANF) antagonizes angiotensin II-induced vascular contractility and aldosterone production in isolated blood vessels and adrenal cells, respectively. To determine the significance of these effects in vivo, the blood pressure and aldosterone responses to synthetic ANF were evaluated in rats with two-kidney, one clip hypertension (n = 5) and in sham-operated controls (n = 4). In the latter, ANF caused a slight fall in mean blood pressure (-7 +/- 3%) and inconsistent changes in plasma renin and aldosterone. In hypertensive rats, ANF decreased blood pressure by 31 +/- 7 mmHg (17 +/- 3%), comparable to the effect of the angiotensin antagonist saralasin (31 +/- 4 mmHg). Plasma renin activity increased from 48 +/- 15 to 79 +/- 23 ng/ml/h. Despite this, ANF caused marked suppression of plasma aldosterone (from 97 +/- 28 to 20 +/- 8.9 ng/100 ml). These results show that ANF can exert potent antihypertensive and aldosterone-lowering effects in vivo, at least when the renin-angiotensin system is stimulated.

Topics: Aldosterone; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Drug Evaluation, Preclinical; Hypertension, Renovascular; Male; Mineralocorticoid Receptor Antagonists; Rats; Rats, Inbred Strains; Renin; Saralasin