atrial-natriuretic-factor and Weight-Gain

Endogenous ouabain (EO)-like compounds are synthesized in and released from the adrenal gland. Although EO has been implicated in several pathological states such as hypertension and heart and kidney failure, its physiological roles in normal animal have not been elucidated. To address this issue, we studied the effects of reduction in plasma EO resulting from antiouabain antibody administration. Normal rats were treated for 28 days with antiouabain antibodies or rabbit IgG as control. Infusions were delivered through a jugular vein cannula by osmotic pumps, and blood pressure was monitored by tail-cuff plethysmography. The animals were housed in metabolic cages to measure water and food consumption and urine excretion. After 28 days, the thoracic aorta was isolated and used to study phenylephrine-induced contraction and atrial natriuretic peptide (ANP)-induced vasorelaxation. The adrenal gland cortex was enlarged in the antiouabain antibody-treated rats. Moreover, on the second day of treatment, there was a significant transient reduction in natriuresis in the antiouabain antibody-treated rats, suggesting that EO is a natriuretic hormone. Reduction in natriuresis was also observed when EO levels were reduced by active immunization resulting from sequential injection of ouabain-albumin. Furthermore, following 28 days of treatment, the response to phenylephrine was significantly lowered and that to ANP was significantly increased in aortic rings from antiouabain antibody-treated rats. These findings show for the first time that circulatory ouabain plausibly originating in the adrenal has physiological roles controlling vasculature tone and sodium homeostasis in normal rats.

Topics: Adrenal Cortex; Aldosterone; Animals; Antibodies; Aorta, Thoracic; Atrial Natriuretic Factor; Blood Pressure; Cardenolides; Corticosterone; Dose-Response Relationship, Drug; Homeostasis; Infusions, Intravenous; Kidney; Male; Natriuresis; Phenylephrine; Rabbits; Rats; Rats, Wistar; Saponins; Sodium; Sodium-Potassium-Exchanging ATPase; Time Factors; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Weight Gain

Inhibition of the renin angiotensin aldosterone system (RAAS) produces protective effects on cardio-renal injury in type 2 diabetes. Vasopeptidase inhibitors (VPI) represent a new pharmacological tool, acting by simultaneous inhibition of the RAAS and neutral endopeptidase. We examined the effects of chronic VPI on renal function and morphology in experimental type 2 diabetes as compared to angiotensin converting enzyme inhibition (ACE-I). Zucker diabetic fatty rats aged 13 weeks were treated with either VPI (AVE7688, ZDF-VPI, n = 8) or ACE-I (Ramipril, ZDF-ACE-I, n = 7) or placebo (ZDF, n = 8). Heterozygous rats served as non-diabetic controls (Ctr, n = 8). Both treatments led to a similar decrease in blood pressure. After 10 weeks of treatment, ZDF developed marked albuminuria. The latter was significantly attenuated in ZDF-VPI as compared to ZDF and ZDF-ACE-I. Renal histology revealed a significant expansion in the glomerular tuft area in all ZDF groups. However, expression of glomerular desmin, which has been recognized as a sensitive marker of early podocyte damage, was significantly increased in ZDF as compared to Ctr. Desmin was reduced in ZDF-VPI but not in animals treated with ACE-I. There was a correlation between albumin excretion and desmin-positive glomerular area. In experimental type 2 diabetes, albuminuria correlates to podocyte damage. These hallmarks of diabetic nephropathy are attenuated by VPI to a greater extent than by ACE-I alone. These findings suggest that podocyte damage is an early critical step in the progression of diabetic nephropathy, and that VPI is a promising pharmacological tool in the treatment of diabetic renal disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Glucose; Blood Pressure; Diabetes Mellitus, Experimental; Heterocyclic Compounds, 3-Ring; Male; Microscopy, Polarization; Neprilysin; Podocytes; Protease Inhibitors; Proteinuria; Ramipril; Rats; Rats, Zucker; Renin-Angiotensin System; Triglycerides; Weight Gain

In this study, semiquantitative reverse transcription-PCR analysis showed that estrogen receptor alpha (ERalpha) and beta (ERbeta) mRNAs are developmentally regulated in the rat heart. We found that ERalpha mRNA was low in all heart chambers of 4-day-old rats, but was elevated in the atria (6- to 18-fold) and ventricles (3- to 4-fold) of adult rats. Western blotting analysis confirmed that these differences were efficiently translated into 67-kDa ERalpha protein. ERbeta mRNA was expressed at its highest level in the left atrium and was 3- to 4-fold lower in other heart chambers of 4-day-old animals. In adult rats ERbeta was decreased dramatically in the left atrium (20-fold) and, to a lesser extent in the other heart chambers (2- to 4-fold). Significant ER changes occurred already in the first week after birth. Accordingly, estrogen regulation in cells from neonatal hearts, as reported in several studies, may not correspond to that occurring in fully differentiated adult hearts, because of an altered degree of ER expression. In adult rats, ovariectomy decreases atrial ERalpha, the atria/body weight ratio, and atrial natriuretic peptide (ANP) transcription. Treatment of ovariectomized rats with 17-beta-estradiol (25 microg, 10 days, s.c.) reversed these changes. In addition, there was no effect of ovariectomy and 17-beta-estradiol supplementation on systolic blood pressure, but in ovariectomized rats a decreased heart rate followed 17-beta-estradiol administration. Similar to the effects on ERalpha in the atria, ovariectomy lowered plasma ANP levels, and 17-beta-estradiol administration restored ANP in the plasma of ovariectomized rats. Changes in plasma ANP correlated with changes in ANP content in the right atrium, as demonstrated by RIA. Increased ANP expression and secretion in response to ERalpha activation may be a protective mechanism in the heart.

Topics: Animals; Animals, Newborn; Atrial Natriuretic Factor; Blood Pressure; Body Weight; DNA Primers; Embryo Implantation; Estradiol; Estrogen Receptor beta; Female; Heart; Heart Rate; Male; Myocardium; Organ Size; Ovariectomy; Pregnancy; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Ribosomal, 16S; Weight Gain

Preascitic cirrhotic patients receiving 200 mmol of sodium daily for seven days remain in positive sodium balance. Thereafter, sodium handling is unknown.. To assess renal sodium handling in preascitic cirrhosis on a high sodium diet for five weeks.. Sixteen biopsy proven preascitic cirrhotics were assessed at weekly intervals for five weeks on a diet of 200 mmol sodium/day using a daily weight diary and weekly 24 hour urinary sodium estimations. Fasting supine neurohormone levels were measured at baseline and weekly for five weeks while haemodynamics were measured at baseline and at five weeks.. The daily diet of 200 mmol of sodium resulted in weight gain and a positive sodium balance for three weeks, associated with significant suppression of plasma renin activity and aldosterone levels, and a significant rise in plasma atrial natriuretic peptide levels (p<0.05). Patients' weights plateaued during week 4, associated with complete sodium balance and significant suppression of plasma noradrenaline levels (p<0.05). This was followed by a negative sodium balance and weight loss, and finally complete sodium balance, again despite a mean net gain of 2.3 (0.3) kg, associated with a return of plasma renin activity and aldosterone levels to within normal ranges. The lack of increase in central blood volume in addition to the persistent increase in plasma atrial natriuretic peptide levels indicated that residual volume expansion, consequent to persistent weight gain, was distributed on the venous side of the circulation. No free fluid was seen on repeat abdominal ultrasound after five weeks.. Preascitic cirrhotics have a natriuretic "escape" after three weeks on high sodium dietary intake, associated with elevated plasma atrial natriuretic peptide levels and suppression of the renin-angiotensin-aldosterone system. With continued suppressed sympathetic activity, preascitics re-establish complete sodium balance but with a net weight gain and presumed increased intravascular volume, but without ascites. This further elucidates the compensated sodium retaining abnormality that characterises preascitic cirrhosis.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Volume; Female; Homeostasis; Humans; Kidney; Liver Cirrhosis; Male; Middle Aged; Norepinephrine; Renin; Sodium; Sodium, Dietary; Time Factors; Weight Gain

In previous studies we demonstrated that in normotensive rats, but not in spontaneously hypertensive rats (SHR), atrial natriuretic peptide (ANP) enhances bradycardic reflexes through an action on cardiac vagal afferent pathways. The present study aimed to determine whether cardiac hypertrophy, hypertension, or a nonreversible genetic factor accounted for the insensitivity of SHR to ANP action on cardiac reflex pathways. SHR were treated with the angiotensin-converting enzyme (ACE) inhibitor perindopril (3 mg/kg per day) for 6 weeks from 4 to 9 weeks of age (SHR-S, n=10) or for 9 weeks from 4 to 12 weeks of age (SHR-L, n=10) or were untreated (SHR, n=10) to produce differential effects on blood pressure and left ventricle/body weight ratio (LV/BW). Untreated normotensive Wistar-Kyoto rats (WKY, n=10) were also studied. At 13 weeks of age, all rats were instrumented with aortic and jugular catheters, and at 14 weeks we measured heart rate reflexes to rapid intravenous infusions of methoxamine (100 microg/kg, cardiac baroreflex) and serotonin (5 to 60 microg/kg, von Bezold-Jarisch cardiac chemosensitive reflex), with either alpha-rat ANP (150 ng/kg per minute IV) or saline vehicle (270 microL/h IV) infusion. Perindopril treatment for 6-week (SHR-S) and 9-week (SHR-L) durations maintained blood pressure at normotensive levels in both groups. SHR-S exhibited a small degree of cardiac hypertrophy (LV/BW was 8% higher than in WKY but 11% less than in untreated SHR), but LV/BW was normalized in SHR-L (to within 1% of WKY LV/BW). In WKY, ANP significantly (P<0.05) enhanced bradycardic responses to both the cardiac baroreflex (by 42+/-10%) and von Bezold-Jarisch chemosensitive reflex (by 17+/-5%) activation but had no effect in SHR. The cardiac reflex action of ANP was restored in SHR-L (ANP enhanced reflex bradycardia by 28+/-12% and 36+/-8%, baroreflex and von Bezold-Jarisch reflex, respectively; P<0.05), but SHR-S, which developed some cardiac hypertrophy, remained unresponsive to ANP. Our results suggest that the inability of ANP to sensitize cardiac vagal (nonarterial) afferents in SHR was not due to an inherited irreversible component, or the hypertension per se, but was associated with the presence of cardiac hypertrophy. A functional consequence of hypertension-induced cardiac hypertrophy may be the inhibition of the cardioprotective action of ANP through cardiac vagal reflexes.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Baroreflex; Blood Pressure; Bradycardia; Cardiomegaly; Heart Rate; Hypertension; Indoles; Male; Perindopril; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Species Specificity; Weight Gain

Littermate male Wistar specific pathogen-free rats were divided into three groups at 28 days of age. The pathophysiological effects seen in rats exposed to normobaric hypoxia (NB) at 10% O2 were compared with those seen in animals exposed to hypobaric hypoxia (HB) at 500 mbar, equivalent to an inspired O2 concentration of 10%, and controls after periods of 5, 10 and 14 days. 5 days' exposure to a low oxygen environment resulted in less weight gain, the development of right ventricular hypertrophy and double elastic laminae in the pulmonary arterioles and an increase in haematocrit and plasma levels of atrial natriuretic peptide (ANP) in both the HB and NB animals compared to controls. There was no significant difference in these values between the two hypoxic groups. After 10 days' exposure to a low oxygen environment, body weight, ventricular ratio, plasma ANP levels and double elastic laminae were higher than the levels seen after 5 days in both NB and HB groups of rats. At day 14 only body weight and haematocrit were greater when compared to day 10 values in NB and HB groups. In conclusion the stress of this hypobaric environment caused no additional changes in the pathophysiological variables studied, compared with the changes seen in NB.

Topics: Animals; Atmospheric Pressure; Atrial Natriuretic Factor; Elastic Tissue; Hematocrit; Hypertension, Pulmonary; Hypoxia; Male; Myocardium; Organ Size; Pulmonary Artery; Rats; Rats, Wistar; Weight Gain

Atrial natriuretic peptide (ANP) concentrations were determined by radioimmunoassay technique in 23 women, 11 women with premenstrual syndrome (PMS) and 12 comparable asymptomatic women. The asymptomatic women showed no change in ANP concentration during the menstrual cycle. In the PMS group ANP levels showed a significant fall in the midluteal phase compared to levels in the follicular phase. Throughout the cycle ANP concentrations were lower in the PMS group than in the comparison group. This difference was statistically significant in the early, mid and late luteal phases of the cycle. The lower ANP concentration in the PMS group in the luteal phases may indicate either a lower plasma volume or a decrease in the total body sodium content or both. These findings are contrary to those expected.

Topics: Adult; Atrial Natriuretic Factor; Female; Follicular Phase; Humans; Luteal Phase; Premenstrual Syndrome; Radioimmunoassay; Water-Electrolyte Balance; Weight Gain