atrial-natriuretic-factor and Hypertension--Portal

Aside from its established immunologic and hematologic functions, the spleen also plays an important role in cardiovascular regulation. This occurs through changes in intrasplenic microvascular tone, as well as through splenic neurohormonal modulation of the renal and mesenteric vascular beds. Splenic regulation of blood volume occurs predominantly through fluid extravasation from the splenic circulation into lymphatic reservoirs; this is controlled by direct modulation of splenic pre- and postcapillary resistance by established physiologic agents such as atrial natriuretic peptide (ANP), nitric oxide (NO), and adrenomedullin (ADM). In addition to physiologic fluid regulation, splenic extravasation is a key factor in the inability to maintain adequate intravascular volume in septic shock. The spleen also controls renal microvascular tone through reflex activation of the splenic afferent and renal sympathetic nerves. This splenorenal reflex not only contributes to the physiologic regulation of blood pressure, but also contributes to the cardiovascular dysregulation associated with both septic shock and portal hypertension. In septic shock, the splenorenal reflex protectively limits splenic extravasation and potentially promotes renal sodium and water reabsorption and release of the vasoconstrictor angiotensin II; this function is eventually overwhelmed as shock progresses. In portal hypertension, on the other hand, the splenorenal reflex-mediated reduction in renal vascular conductance exacerbates sodium and water retention in the kidneys and may eventually contribute to renal dysfunction. Preliminary evidence suggests that the spleen also may play a role in the hemodynamic complications of portal hypertension via neurohormonal modulation of the mesenteric vascular bed. Lastly, the spleen itself may be a source of a vasoactive factor.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension, Portal; Kidney; Nitric Oxide; Shock, Septic; Splanchnic Circulation; Spleen

Patients with cirrhosis and ascites have high plasma levels of atrial natriuretic peptide (ANP). Pharmacological doses of this hormone usually worsen systemic hemodynamics of cirrhotic patients. We assessed whether ANP influences cardiovascular homeostasis and renal function in patients with compensated cirrhosis at plasma levels comparable to those observed in patients with cirrhosis and ascites.. Radionuclide angiocardiography was performed in eight compensated cirrhotic patients during placebo (three periods of 15 min each) and ANP infusion (2, 4, and 6 pmol/kg.min for 15 min each), together with appropriate blood and urine sampling, to evaluate left ventricular diastolic, systolic, and stroke volume, heart rate, cardiac output, arterial pressure, peripheral vascular resistance, creatinine clearance, urinary sodium excretion, plasma renin activity, plasma aldosterone, norepinephrine and hematocrit.. The infusion increased plasma ANP up to levels (52.03 +/- 2.29 pmol/L) comparable with those observed in 35 patients with ascites (46.42 +/- 1.57 pmol/ L). This increment was associated with significant reductions in left ventricular end diastolic volume, stroke volume, cardiac index (from 3.7 +/- 0.7 to 3.1 +/- 0.5 L/min.m2, p < 0.05) and mean arterial pressure (from 96.7 +/- 6.5 to 88.5 +/- 9.5 mmHg, p < 0.05), while heart rate and hematocrit significantly increased. Peripheral vascular resistance did not change. These hemodynamic effects occurred despite significant increases in plasma renin activity and norepinephrine. ANP also induced increases in creatinine clearance, urinary sodium excretion, and fractional sodium excretion.. Low-dose ANP affected cardiovascular homeostasis and renal sodium handling in compensated cirrhosis, suggesting that this hormone may be involved in the pathophysiology of systemic hemodynamic and renal functional abnormalities of cirrhosis.

Topics: Aldosterone; Analysis of Variance; Ascites; Atrial Natriuretic Factor; Creatinine; Cyclic GMP; Female; Hematocrit; Hemodynamics; Humans; Hypertension, Portal; Infusions, Intravenous; Kidney; Kidney Function Tests; Liver Cirrhosis; Middle Aged; Natriuresis; Norepinephrine; Renin

The effect of spironolactone on esophageal variceal pressure (VP) in patients without ascites was investigated. VP was assessed using a noninvasive endoscopic gauge. Spironolactone was administered during a 6-week period at a dosage of 100 mg/d. This treatment decreased VP from 16.8 +/- 1.9 (SD) to 14.1 +/- 2.7 mm Hg (P < .001) in a group of 12 patients and from 18.6 +/- 2.1 to 13.7 +/- 4.1 mm Hg (P < .01) in another group of 8 patients who still had high VP despite chronic intake of propranolol. In both groups, placebo administration to 12 and 8 comparable patients did not significantly alter VP. Spironolactone induced a significant reduction of plasma volume (42.1 +/- 5.5 to 36.1 +/- 6.6 mL/kg body weight, P < .01) and of the concentration of alpha-atrial natriuretic peptide (alpha-ANP) (39.8 +/- 22 to 27.7 +/- 20 pg/mL, P < .01); in addition, a pronounced increase in plasma renin activity (PRA) (1.1 +/- 0.9 to 7.5 +/- 3.4 ng/mL/h, P < .001) was induced by the treatment. No significant changes in systemic hemodynamics were observed during the studies. Severe side effects were not observed except for a high incidence (55%) of painful gynecomasty in the male patients. In conclusion, chronic spironolactone administration effectively lowers VP, even in patients under chronic propranolol therapy. The combination of propranolol and spironolactone deserves further study as a prophylactic therapy of variceal hemorrhage, but development of gynecomasty might be a problem. Finally, we confirmed the reproducibility of VP measurements with the noninvasive gauge in chronic conditions.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Analysis of Variance; Ascites; Atrial Natriuretic Factor; Blood Pressure; Diuretics; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Plasma Volume; Propranolol; Renin; Reproducibility of Results; Spironolactone

We investigated left ventricular diastolic dysfunction (LVDD) and its relationship with circulatory function and prognosis in cirrhosis with portal hypertension and normal creatinine. Conventional and tissue Doppler (TDI) echocardiography, systemic and hepatic hemodynamics, and the activity of endogenous vasoactive systems (AEVS) were measured prospectively in 80 patients. Plasma renin activity (PRA; >4 ng/mL/hour) was used as a surrogate of effective arterial blood volume. Patients were followed up for 12 months. Thirty-seven patients had LVDD (19 with grade 1 and 18 with grade 2). Left ventricular hypertrophy, left atrial volume, AEVS, and natriuretic peptide levels were significantly greater in patients with LVDD than without LVDD. Patients with grade 2 LVDD, compared to grade 1 LVDD and without LVDD, had significantly lower mean arterial pressure and higher Model for End-Stage Liver Disease (MELD) score, E-wave transmitral/early diastolic mitral annular velocity (E/e' ratio), cardiopulmonary pressures, PRA, and natriuretic peptide levels. Systolic and cardiac chronotropic function were significantly lower in patients with grade 2 LVDD than without LVDD. LVDD was more frequent in patients with ascites and increased PRA than patients without ascites or with ascites but normal PRA. Fourteen patients with LVDD developed hepatorenal syndrome (HRS) type 1 on follow-up. Survival was different according to degree of LVDD (without LVDD: 95%; grade 1 LVDD: 79%; grade 2 LVDD: 39%; P < 0.001). Independent predictive factors of mortality were MELD score and E/e' ratio.. LVDD occurs simultaneously with other changes in cardiac structure and function and is associated with an impairment of effective arterial blood volume. LVDD is a sensitive marker of advanced cirrhosis, type 1 HRS development, and mortality.

Topics: Adult; Atrial Natriuretic Factor; Creatinine; Diastole; Female; Heart Rate; Hepatorenal Syndrome; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Prospective Studies; Renin; Severity of Illness Index; Ventricular Dysfunction, Left

In liver cirrhosis atrial natriuretic peptide (ANP) decreases portal vascular resistance and tributary flow. The enzyme neutral endopeptidase (NEP) degrades ANP and bradykinin and generates endothelin-1 from big-endothelin. We determined the effects of NEP inhibition by candoxatrilat on hormonal status, liver function and arterial and portal pressures in rats with CCl4-induced cirrhosis.. Two groups of seven control rats received 1 ml 5% glucose solution alone or containing 10 mg/kg candoxatrilat; three groups of 10 ascitic cirrhotic rats received placebo, 5 or 10 mg/kg candoxatrilat. NEP protein concentration and immunostaining were analyzed in normal and cirrhotic livers.. In cirrhotic rats 10 mg/kg candoxatrilat significantly increased steady-state indocyanine green clearance (a parameter reflecting liver plasma flow) (P<0.01), decreased portal pressure (P<0.01), had no effect on arterial pressure and plasma renin activity but increased ANP plasma levels (P<0.05) and urinary excretions (P<0.01) of ANP and cGMP. In the cytosol fraction of rat cirrhotic livers a 280% increase in NEP content was found (P<0.01), chiefly localized in desmin-positive myofibroblast-like cells of fibrous septa.. Candoxatrilat has few effects on systemic hemodynamics and hormonal status; its portal hypotensive action depends on effects exerted on intrahepatic vascular resistance.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Carbon Tetrachloride; Cyclic GMP; Cyclohexanecarboxylic Acids; Cytokines; Endothelin-1; Humans; Hypertension, Portal; Liver; Liver Cirrhosis, Experimental; Male; Neprilysin; Portal Vein; Protease Inhibitors; Rats; Rats, Wistar; Vascular Resistance

The spleen is an important site of atrial natriuretic factor (ANF)-induced fluid extravasation into the systemic lymphatic system. The mechanism underlying this process was studied in a blood-perfused (1 ml min(-1)) rat spleen using the double occlusion technique. To ensure that our observations were spleen specific, a similar protocol was repeated in the hindquarters. Rat ANF(1-28), infused into the splenic artery of anaesthetized male rats, caused a dose-dependent (0.3-59 pmol min(-1)) increase in microvascular pressure from 11.3 +/- 0.7 to 14.9 +/- 0.5 mmHg and in post-capillary resistance from 7.2 +/- 0.6 to 10.1 +/- 1.1 mmHg ml(-1). ANF elicited no change in splenic pre-capillary resistance or in hindquarter haemodynamics. Intrasplenic ANF (6.5 pmol min(-1)) caused a sustained increase in intrasplenic fluid efflux from 0.1 +/- 0.1 to 0.3 +/- 0.1 ml min(-1), and in capillary filtration coefficient (Kf) from 1.2 +/- 0.5 to 2.4 +/- 0.6 ml mmHg-1 min-1 (100 g tissue)-1. Mechanical elevation of splenic intravascular pressure (from 11.3 +/- 0.7 to 22.4 +/- 0.2 mmHg) significantly increased intrasplenic fluid extravasation (from 0.4 +/- 0.3 to 1.4 +/- 0.3 ml min(-1)). The natriuretic peptide receptor-C (NPRC)-specific agonist C-ANF(4-23) (12.5 and 125 pmol min(-1)) did not alter splenic intravascular pressure or pre-/post-capillary resistance. The ANF antagonist A71915 (8.3 and 83 pmol min-1), which blocks ANF-stimulated cGMP production via natriuretic peptide receptor-A (NPRA), inhibited the ANF-induced changes in splenic microvascular pressure and post-capillary resistance. It is concluded that ANF enhances the extravasation of isoncotic fluid from the splenic vasculature both by raising intrasplenic microvascular pressure (increased post-capillary resistance) and by increasing filtration area. The constrictive activity of ANF on the splenic vasculature is mediated through NPRA.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Body Fluids; Dose-Response Relationship, Drug; Hindlimb; Hypertension, Portal; Male; Microcirculation; Portal Vein; Rats; Rats, Long-Evans; Spleen; Splenic Artery; Vascular Resistance; Water-Electrolyte Balance

In cirrhosis, the effects of selective activation of atrial natriuretic peptide (ANP) R2-receptors on haemodynamics, endogenous ANP (ANP1-28) and sodium excretion are unknown. The aim of the present study was to examine the effects of selective activation of ANP-R2 receptors by ANP4-23 (a ring-deleted analogue of endogenous ANP) on haemodynamics, plasma ANP1-28 concentrations and urinary sodium excretion in conscious cirrhotic and normal rats.. Haemodynamics and sodium excretion were measured prior to and following administration of ANP4 23. Plasma ANP1-28 concentrations were also measured.. In cirrhotic rats, ANP4-23 significantly decreased portal pressure and tributary blood flow by 15% and 25% respectively but significantly increased portal territory vascular resistance by 30%. Systemic and renal haemodynamics were not altered by ANP4-23. In normal rats, ANP4-23 did not significantly change splanchnic, renal and systemic haemodynamics. In both groups of rats, ANP4-23 increased plasma ANP1-28 concentrations but did not change sodium excretion.. ANP4-23 administration induced splanchnic vasoconstriction in cirrhotic but not in normal rats. ANP4-23-elicited vasoconstriction caused a portal hypotensive effect in cirrhotic rats. Finally, in both groups, ANP4-23 caused an increase in plasma ANP1-28 concentrations but did not increase sodium excretion.

Topics: Animals; Atrial Natriuretic Factor; Guanylate Cyclase; Hemodynamics; Hypertension, Portal; Kidney; Liver Cirrhosis, Experimental; Male; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Sodium; Splanchnic Circulation

In portal hypertension, the role of the vasorelaxant nitric oxide (NO) in long-term splanchnic and systemic vascular tone regulation is unclear. This study examined the effects of long-term administration of a NO synthesis inhibitor on haemodynamics in portal hypertensive rats. Rats were randomly assigned to receive either water (placebo) or 100 mg/kg.day of oral N-nitro-L-arginine methylester (L-NAME) for 28 days. At 14 days, the portal vein was ligated in 10 rats from each group. At 28 days, splanchnic and systemic blood flows were measured in 20 normal and 20 portal vein stenosed rats. Plasma atrial natriuretic peptide (ANP) concentrations as well as plasma and urinary cyclic guanosine monophosphate (cGMP) levels were also measured. Porto-systemic shunts were measured in other portal vein stenosed animals that had or had not received L-NAME. Portal vein stenosed rats that received L-NAME had significantly lower portal tributary blood flow and percentages of portal-systemic shunting (7.3 +/- 0.5 versus 3.7 +/- 0.2 ml/min.100 g and 96 +/- 1 versus 68 +/- 5%, respectively) and higher hepatocollateral vascular resistance (147 +/- 10 versus 295 +/- 30 dyn.s.cm-5.100 g.10(3), respectively) than placebo portal vein stenosed rats. Portal pressure, ANP and cGMP levels did not differ between the groups. Arterial pressure was significantly higher and cardiac index lower after L-NAME than after placebo. Normal rats had similar but less marked L-NAME-induced responses than portal hypertensive rats. The presence of a long-term L-NAME-induced vasoconstriction in collateral vessels and splanchnic and systemic arterioles in portal vein stenosed rats indicates that a NO-mediated vasodilator tone may contribute to the development and the maintenance of collateral circulation as well as splanchnic and systemic vasodilation in portal hypertension. Moreover, the NO-mediated vasodilator tone in portal hypertensive animals seems to be increased.

Topics: Animals; Atrial Natriuretic Factor; Cyclic GMP; Enzyme Inhibitors; Hemodynamics; Hypertension, Portal; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Rats; Rats, Sprague-Dawley; Vasoconstriction

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Echocardiography; Female; Heart; Hemodynamics; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Renin; Stroke Volume

It has been postulated that one of the mechanisms of hypotension associated with cirrhosis is an attenuated responsiveness to catecholamines despite the increased activity of the sympathetic nervous system and the elevated plasma concentrations of the sympathetic neurotransmitter, norepinephrine. This abnormality was studied in a dog model of portal hypertension and cirrhosis. Twelve weeks after bile duct ligation (n = 16), intrasplenic pressure rose significantly from 6.3 +/- 0.4 to 14.6 +/- 1.6 mmHg (p < 0.05), mean arterial pressure had fallen from 106 +/- 4 to 83 +/- 8 mmHg (p < 0.01), cardiac output had risen from 3.1 +/- 0.2 to 3.8 +/- 0.8 l/min (p < 0.05) and plasma norepinephrine concentrations rose from 0.22 +/- 0.12 to 1.17 +/- 0.52 nmol/l (p < 0.05). In 7 sham-operated dogs, the changes in these 4 variables over the same period were non-significant. In vivo pressor responsiveness was tested by studying the effects of intravenous and intra-arterial infusions of norepinephrine and the non-selective beta-adrenoceptor agonist, isoproterenol. In vitro responsiveness was tested by measuring the effects of isoproterenol on the isometric twitch of isolated ventricular strips and the effects of norepinephrine on femoral, mesenteric and renal arterial rings. There was no significant change in the in vivo responses of chronic bile-duct-ligated dogs at 12 weeks compared to the preoperative assessment, or to sham-operated dogs at 12 weeks. Furthermore, there was no significant difference between the in vitro responses of ventricular strips to isoproterenol or arterial rings to norepinephrine prepared from chronic bile-duct-ligated and sham-operated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aldosterone; Animals; Arteries; Atrial Natriuretic Factor; Bile Ducts; Bilirubin; Blood Pressure; Dogs; Dose-Response Relationship, Drug; Hypertension, Portal; Hypotension; In Vitro Techniques; Isoproterenol; Liver Cirrhosis, Experimental; Liver Function Tests; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Plasma Volume; Reference Values; Renin; Serum Albumin; Sodium; Sodium, Dietary; Time Factors

The aim of this study was to assess the effects of an oral dose (20 mg) of isosorbide-5-mononitrate on systemic hemodynamics, kidney function, plasma renin activity and plasma aldosterone and atrial natriuretic peptide concentrations in 16 nonazotemic cirrhotic patients. Isosorbide-5-mononitrate significantly reduced cardiopulmonary pressures, cardiac output, peripheral vascular resistance, mean arterial pressure, renal plasma flow, glomerular filtration rate, free water clearance, sodium excretion and atrial natriuretic peptide concentration and significantly increased renin and aldosterone values. Cardiopulmonary pressures, atrial natriuretic peptide, cardiac output and mean arterial pressure decreased to a similar extent in patients with (n = 9) and without ascites (n = 7). In patients with ascites we noted marked increases in plasma renin activity (3.7 +/- 1.1 ng/ml/hr to 6.4 +/- 1.8 ng/ml/hr; p = 0.01) and aldosterone level (61.1 +/- 17.5 ng/dl to 108.4 +/- 36.1 ng/dl; p = 0.01). In contrast, in patients without ascites the elevation of plasma renin activity (0.5 +/- 0.16 ng/ml/hr to 0.95 +/- 0.27 ng/ml/hr; p = 0.02) and aldosterone level (5.9 +/- 1.3 ng/dl to 12.3 +/- 3.8 ng/dl; p = 0.02) was mild, and in no case did these parameters increase over the upper normal limit. Isosorbide-5-mononitrate produced a significantly greater reduction of glomerular filtration rate (-21.4% +/- 3.3% vs. -8.9% +/- 4.2%; p = 0.03) and free water clearance (-82.4% +/- 16.1% vs. -34.5% +/- 12.3%; p = 0.03) in patients with ascites than in those without.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aldosterone; Ascites; Atrial Natriuretic Factor; Hemodynamics; Humans; Hypertension, Portal; Isosorbide Dinitrate; Kidney; Liver Cirrhosis; Renin

The atrial natriuretic peptide hormonal system is altered to a variable degree in patients with cirrhosis. Portal pressure and portal-systemic shunting are also varied in cirrhosis. We used a portal vein-ligated rat model with predictable portal hypertension to study the effects of portal hypertension alone on the atrial natriuretic peptide hormonal system. Sham-operated rats were used as controls. Mean portal pressure was significantly increased in portal vein-ligated rats (portal vein-ligated rats, 21.7 +/- 0.74 cm H2O; sham-operated rats, 13.7 +/- 0.47 cm H2O; p less than 0.0001). Plasma atrial natriuretic peptide decreased 50% in the portal vein-ligated rats (p less than 0.0001). Atrial natriuretic peptide messenger RNA level was decreased by 40% to 60% in the left and right atria and in the ventricles of portal vein-ligated rats (p less than 0.05 for each chamber). Only one class of glomerular binding site was identified by competitive binding studies. The atrial natriuretic peptide glomerular receptor density increased in the portal vein-ligated rats (portal vein-ligated rats, 1,660 +/- 393; sham-operated 725 +/- 147 fmol/mg protein, p less than 0.02), whereas affinity decreased (portal vein-ligated, 1.69 +/- 0.49; sham-operated, 0.55 +/- 0.12 nmol/L, p less than 0.02). No difference was seen in the amount of cyclic GMP generated by atrial natriuretic peptide stimulation in isolated glomeruli from portal vein-ligated and sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Binding, Competitive; Blood Pressure; Cyclic GMP; Hypertension, Portal; In Vitro Techniques; Kidney Glomerulus; Ligation; Male; Myocardium; Portal Vein; Rats; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Stimulation, Chemical

Despite intensive investigation, the pathogenesis of sodium retention in patients with chronic liver disease is not fully known. We have studied 19 chronic liver disease patients, 13 without (group 1) and six with (group 2) histories of clinical sodium retention (ascites or edema) by varying dietary sodium intake. The patients were placed on a 20 mmol/day constant diet for 1 wk, followed by a constant 100 mmol/day sodium diet for 1 wk under strict metabolic conditions. After 5 days of equilibration on each diet, blood and urine samples were collected for plasma atrial natriuretic factor levels and urinary sodium excretion. Group 1 patients (n = 6) achieved near sodium balance in 5 days on both a 20-mmol (urinary sodium output = 17 +/- 3 mmol/day) and a 100-mmol sodium diet (urinary sodium output = 80 +/- 5 mmol/day). Atrial natriuretic factor levels in these patients tended to be elevated, but the increase was not significantly greater than that in normal control subjects (10 +/- 4 pg/ml to 19 +/- 4 pg/ml) on the same diets. In contrast, group 2 patients (n = 5) were in significant positive sodium balance on both the 20 mmol/day sodium diet (mean urinary sodium output = 9.5 +/- 3.3 mol/day) and the 100 mmol/day sodium diet (urinary sodium output = 37 +/- 13 mmol/day). This occurred despite significantly elevated baseline atrial natriuretic factor levels and a significant increase in plasma atrial natriuretic factor levels after sodium challenge (62 +/- 9 pg/ml, p less than 0.05) on a 100 mmol/day sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ascites; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Edema; Heart Atria; Humans; Hypertension, Portal; Kidney; Liver Cirrhosis; Sodium; Sodium, Dietary; Time Factors

Topics: Animals; Atrial Natriuretic Factor; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Cirrhosis, Experimental; Natriuresis; Rats; Vasopressins

The effect of atrial natriuretic polypeptide (ANP) on hemodynamics and renal function was evaluated after the reconstructive surgery of the left renal artery in a patient with renovascular hypertension secondary to Takayasu's arteritis. The reconstructive surgery was done using the femoral artery, since we were unable to obtain adequate vein segments to fit the renal artery. The femoral artery was reconstructed by her saphenous vein segments. After 30 min of the aortorenal bypass operation, alpha-human ANP (alpha-hANP) was infused intravenously for 10 min at a rate of 0.1 microgram/kg/min. Although total peripheral resistance was decreased by alpha-hANP infusion, blood pressure was not changed because of the increased cardiac output. Glomerular filtration rate was increased markedly with concomitant increase in urine volume and urinary excretions of sodium, potassium and phosphate. Fractional excretions of water and sodium were not changed, but fractional excretion of phosphate and potassium clearance were increased. Thus, the infusion of alpha-hANP markedly improved the renal function of the ischemic kidney by the reconstructive surgery of the renal artery, suggesting that alpha-hANP seems clinically applicable as a protective agent in renal ischemia at renovascular surgery as well as the renal transplantation.

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Hypertension, Portal; Ischemia; Postoperative Complications; Radiography

The effects of atrial natriuretic factor (ANF) on splanchnic hemodynamics and renal function in portal hypertensive models are described incompletely. Furthermore, ANF-induced vasodilatation and hypotension may limit the assessment of its own renal physiological effects. We infused ANF (human ANF 102-126) to anesthetized portal vein-ligated rats, a model with prehepatic portal hypertension. Arterial pressure was reduced by 17%, but portal pressure was unaffected. Diuresis and natriuresis were explained in part by an increase in glomerular filtration rate; in addition, renal vascular resistance was significantly decreased. The natriuretic response to ANF was slightly, but significantly, decreased in portal hypertensive rats as compared to controls (fractional excretion of sodium, 1.8 +/- 0.4 vs. 2.9 +/- 0.3; P less than .05). The addition of Phe-Ile-Orn-vasopressin, a V1 receptor agonist, normalized arterial pressure but induced a significant decrease in portal pressure (15 +/- 0.9 mm Hg base line vs. 12.8 +/- 0.7 combination group; P less than .01). Furthermore, the combination of both drugs markedly potentiated the natriuretic effects (0.4 +/- 0.1 microEq/min of control vs. 10.0 +/- 2.3 ANF vs. 32.2 +/- 3.3 combination group; P less than .001). The natriuretic potentiation resulted from increments in glomerular filtration rate and renal blood flow. Normalization of arterial pressure may enhance the renal physiological effects of ANF, in this portal hypertensive model.

Topics: Animals; Atrial Natriuretic Factor; Drug Synergism; Glomerular Filtration Rate; Hemodynamics; Hypertension, Portal; Kidney; Male; Natriuresis; Ornipressin; Rats; Rats, Inbred Strains; Splanchnic Circulation; Vasopressins