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H R Keiser

Publications and source records attributed to H R Keiser.

At least 37 records · Page 2Linked to original sources
PubMed1995

Expression of renin-angiotensin system components in the heart, kidneys, and lungs of rats with experimental heart failure.

BACKGROUND: Chronic activation of the renin-angiotensin system (RAS) plays an important role in the pathogenesis of heart failure. Increasing evidence indicates that other than the circulating RAS, a local RAS exists in several tissues, including the heart. The present study was carried out to quantify cardiac, renal, and pulmonary mRNA levels of renin, angiotensin-converting enzyme (ACE), and types 1 and 2 angiotensin II receptors (AT-1 and AT-2), in rats with different severities of heart failure. METHODS AND RESULTS: Heart failure was induced by the creation of an aortocaval fistula below the renal arteries. Rats with aortocaval fistula either compensate and maintain a normal sodium balance or decompensate and develop severe sodium retention. Six days after placement of the aortocaval fistula, heart weight (normalized to body weight) increased 35% (P < .05) in compensated and 65% in decompensated rats compared with control rats. Plasma renin activity increased 45% (P < .05) in rats in sodium balance and 127% in sodium-retaining rats. Total RNA was extracted from the heart, kidneys, and lungs, followed by reverse transcription-quantitative polymerase chain reaction. Renin mRNA levels in the heart, after 40 cycles, increased 68% (P < .01) and 140% in rats with either compensated or decompensated heart failure, respectively. Renal renin-mRNA levels also increased 130% (P < .05) in decompensated and only 52% (P < .05) in compensated animals. ACE-mRNA increased in a similar pattern in the heart but not in either the kidneys or lungs. Moreover, pulmonary, renal, and cardiac ACE immunoreactivity levels, assessed by Western blot analysis, showed the same trend. AT-1 receptor mRNA levels decreased 54% (P < .05) only in the myocardium of decompensated rats, whereas AT-2 receptor mRNA did not change in any tissue studied. CONCLUSIONS: The development of heart failure is associated with a remarkable increase in the expression of a local RAS in the heart, which may contribute to the pathogenesis of this clinical syndrome.

Angiotensin II↗
PubMed1995

Plasma metanephrines in the diagnosis of pheochromocytoma.

OBJECTIVE: To examine whether tests for plasma metanephrines, the o-methylated metabolites of catecholamines, offer advantages for diagnosis of a pheochromocytoma over standard tests for plasma catecholamines or urinary metanephrines. DESIGN: Cross-sectional study. SETTING: 3 clinical specialist centers. PATIENTS: 52 patients with a pheochromocytoma; 67 normotensive persons and 51 patients with essential hypertension who provided reference values; and 23 patients with secondary hypertension and 50 patients with either heart failure or angina pectoris who served as comparison groups. MEASUREMENTS: Plasma concentrations of catecholamines (norepinephrine and epinephrine) and metanephrines (normetanephrine and metanephrine) were measured in all patients. The 24-hour urinary excretion of metanephrines was measured in 46 patients with pheochromocytoma. RESULTS: Pheochromocytomas were associated with increases in plasma concentrations of metanephrines that were greater and more consistent than those in plasma catecholamine concentrations. No patient with a pheochromocytoma had normal plasma concentrations of both normetanephrine and metanephrine. The sensitivity of these tests was 100% (52 of 52 patients [95% CI, 94% to 100%]), and the negative predictive value of normal plasma concentrations of metanephrines was 100% (162 of 162 patients). Tests for plasma catecholamines yielded eight false-negative results and a sensitivity of 85% (44 of 52 patients [CI, 72% to 93%]). The negative predictive value of normal plasma concentrations of catecholamines was 95% (156 of 164 patients). Tests for urinary metanephrines yielded five false-negative results and a sensitivity of 89% (41 of 46 patients [CI, 76% to 96%]). Because no statistical difference was noted in the number of false-positive results between tests for plasma metanephrines (15%) and tests for plasma catecholamines (18%), the specificities of the two tests did not differ. CONCLUSIONS: Normal plasma concentrations of metanephrines exclude the diagnosis of pheochromocytoma, whereas normal plasma concentrations of catecholamines and normal urinary excretion of metanephrines do not. Tests for plasma metanephrines are more sensitive than tests for plasma catecholamines or urinary metanephrines for the diagnosis of pheochromocytoma.

Adolescent↗
PubMed1995

Effects of angiotensin II and phenylephrine on urinary endothelin in normal female volunteers.

Endothelin (ET) is a 21-amino acid peptide produced and secreted mainly by endothelial cells. Small amounts of ET are found in plasma, whereas large amounts are present in the urine. Despite the abundance of ET in the kidneys and urine, little is known about its regulation and clinical significance. The present study was designed to examine the effects of angiotensin II (Ang II) and phenylephrine (Phe) on the excretion of ET in normal female volunteers. Ang II and Phe were infused for 1 hour each and titrated to increase the mean arterial pressure by 20 mm Hg. There was a 60-minute recovery period before the second drug, and the order of the drugs was randomized. Infusion of Phe induced mild diuresis and natriuresis, which were associated with a significant increase in the excretion of ET. In addition, Phe significantly increased plasma atrial natriuretic factor (ANF). In contrast, infusion of equipressor doses of Ang II decreased urinary sodium excretion and did not significantly alter the excretion of ET. Moreover, Ang II induced only a small and nonsignificant increase in plasma ANF. These results demonstrate that (1) physiological doses of Ang II do not affect excretion of either ET or ANF; (2) Phe markedly increased the excretion of ET and ANF, independently of its effect on blood pressure; and (3) neither agent changed plasma ET, but Phe increased plasma ANF.

Adolescent↗
PubMed1995

Pulmonary and renal neutral endopeptidase EC 3.4.24.11 in rats with experimental heart failure.

Congestive heart failure is characterized by avid sodium retention and a blunted renal response to exogenous and endogenous atrial natriuretic peptide. Inhibition of neutral endopeptidase EC 3.4.24.11, the main enzyme that degrades natriuretic peptides, produces a natriuretic response in different models of congestive heart failure. This raises the possibility that an increase in either the expression or activity of neutral endopeptidase is responsible for these phenomena. In the present study, we examined (1) the renal effects of SQ-28,603, a neutral endopeptidase inhibitor, in rats with moderate and severe congestive heart failure induced by an aortocaval fistula compared with sham controls, and (2) neutral endopeptidase expression and activity in the lungs and kidneys of these rats. Infusion of SQ-28,603 (40 mg/kg IV) induced a significant natriuretic response in normal rats and rats with moderate congestive heart failure. This response was blunted in rats with severe congestive heart failure. Surprisingly, renal neutral endopeptidase mRNA levels, assessed by quantitative reverse transcriptase-polymerase chain reaction; protein levels, assessed by Western blotting; and activity, assessed by gelatin gels, were comparable in all groups. Pulmonary neutral endopeptidase mRNA levels decreased by 45% in rats with severe congestive heart failure but not in rats with mild congestive heart failure. In addition, pulmonary neutral endopeptidase immunoreactivity levels and activity were significantly decreased in congestive heart failure in correlation with the severity of the disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1994

Urinary excretion rate of endothelin-1 in patients with essential hypertension and salt sensitivity.

To assess the possible role of ET-1 in the pathogenesis of hypertension and salt sensitivity levels of immunoreactive endothelin-1 (irET-1) were measured in plasma and urine of 17 patients with essential hypertension and in 19 normotensive control subjects. Effects of alterations in dietary sodium content on urinary irET-1 levels also were assessed. Plasma levels of irET-1 did not differ between the hypertensives and normotensive groups (1.1 +/- 0.3 and 1.3 +/- 0.1 pg/ml). Urine samples of both groups contained high concentrations of irET-1. However, the mean daily urinary excretion of irET-1 in the hypertensives was less than one-third that in controls (29 +/- 3 vs. 109 +/- 21 ng/day, respectively, P < 0.01). Changing dietary sodium content in the hypertensives had no effect on mean irET-1 excretion. However, on either low, intermediate, or high salt diet, "salt sensitive" hypertensives had lower levels of the peptide than "salt resistant" patients (23 +/- 3 vs. 36 +/- 5 ng/day, respectively, P < 0.05). The data demonstrate a marked reduction in irET-1 excretion in patients with essential hypertension, despite normal plasma levels of the peptide. Since ET-1 has diuretic and natriuretic properties, the decreased renal excretion of ET-1 may be of relevance to the pathophysiology of hypertension and salt sensitivity.

Adult↗
PubMed1994

Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells.

Recently ouabain has been shown to induce transcription of proto-oncogenes in different cell types. In the present study, we examined the effect of ouabain on the proliferation of cultured vascular smooth muscle cells (VSMCs). Primary aortic VSMCs of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and the rat VSMC cell line A10, were used. Different concentrations of ouabain (10(-9) to 10(-5) mol/L) were added to either quiescent or proliferating cells, and the cell number, the rate of thymidine incorporation into DNA, and the transcription of c-fos and c-myc were examined. The addition of ouabain to proliferating VSMC increased the rate of thymidine incorporation into DNA in a dose-dependent manner, and induced the transcription of the proto-oncogenes within 1 h. This latter response disappeared after 24 h. The number of cells significantly increased in response to low concentrations of ouabain (10(-8) to 10(-7) mol/L), but gradually decreased in response to higher concentrations of the agent, probably due to a toxic effect. Addition of ouabain to quiescent cells, in medium without serum, did not promote cell growth by any of the parameters examined. According to a current theory, endogenous digitalis-like substances possess natriuretic and hypertensive properties, and provide the link between an excessive intake of salt and high blood pressure. The mitogenic effect of ouabain on VSMCs may be a component of this hypertensive action.

Animals↗
PubMed1994

Hydrolysis of iodine labelled urodilatin and ANP by recombinant neutral endopeptidase EC. 3.4.24.11.

1. Urodilatin is a 32 amino-acid peptide of similar sequence to atrial natriuretic peptide (ANP), with four additional amino-acids at the N-terminus. Although ANP and urodilatin bind to the same receptors with similar affinities, urodilatin is more active than ANP as a natriuretic agent. Previous studies, using neutral endopeptidase EC 3.4.24.11 (NEP) derived from crude membrane preparations, were inconclusive, but suggested that urodilatin was more resistant than ANP to degradation by this enzyme. In the present study, we compared the degradation rates of [125I]-urodilatin and [125I]-ANP by pure recombinant NEP (rNEP). 2. Incubation of radioactively labelled ANP with rNEP resulted in a much more rapid degradation of the peptide than that for labelled urodilatin. 3. Both phosphoramidon and SQ-28,603, potent inhibitors of NEP, completely protected both peptides from metabolism by rNEP. 4. The circular dichroism spectra of the two peptides indicate that they are very similar and exist largely in unordered or flexible conformations. 5. These results support the relative resistance of urodilatin to NEP, and indicate that urodilatin may be of use as a therapeutic agent, in conditions in which ANP is ineffective.

Atrial Natriuretic Factor↗
PubMed1994

Angiotensin II maintains, but does not mediate, isoproterenol-induced cardiac hypertrophy in rats.

The role of angiotensin II (ANG II) in the development of isoproterenol (Iso)-induced cardiac hypertrophy was examined in rats. Iso increased cardiac mass, left ventricular RNA-to-DNA ratio, and the cardiac content of both myosin heavy chain and hydroxyproline in a dose-dependent manner, indicating that Iso-induced cardiac hypertrophy involves growth of both muscle and connective tissue. Cardiac hypertrophy reverted within 11-14 days after cessation of Iso. Propranolol prevented development of Iso-induced cardiac hypertrophy but did not affect the rate of its reversal. The ANG II receptor blocker losartan (Los) did not significantly decrease the hypertrophic response to Iso. Los injected after cessation of Iso dramatically enhanced the reversal of cardiac hypertrophy, even in rats that received Los with Iso during the induction of Iso-induced cardiac hypertrophy. ANG II, injected continuously at a subpressor dose that did not affect heart weight when given alone, inhibited reversal of cardiac hypertrophy when given after cessation of Iso. Los did not significantly affect the induction of the protooncogene c-fos by Iso. We conclude that endogenous ANG II has a major function in maintaining Iso-induced cardiac hypertrophy but does not mediate its induction. This suggests that different interactive stimuli may be required for development of cardiac hypertrophy, i.e., for initiation and for maintenance.

Actins↗
PubMed1994

Losartan improves the natriuretic response to ANF in rats with high-output heart failure.

During severe congestive heart failure (CHF), a number of sodium-retaining and vasoconstricting mechanisms are activated, including the renin-angiotensin-aldosterone system. In CHF, the renal effects of atrial natriuretic factor (ANF) are attenuated. The interaction of these endocrine factors is a major determinant of the clinical course of CHF. This study was designed to evaluate the role of the renin-angiotensin-aldosterone system in the development of avid sodium retention in CHF, induced in rats by creation of an aorto-caval fistula. Rats with aorto-caval fistula either compensate and maintain a normal sodium balance (UNaV > 1400 microEq/day) or decompensate and develop severe sodium retention (UNaV < 200 microEq/day), which leads to severe CHF. Chronic treatment with losartan, an angiotensin II receptor blocker, 10 mg/day, resulted in dramatic natriuresis (UNaV > 1000 microEQ/day) in decompensated rats, but not in compensated rats or controls. ANF infusion (50 micrograms/kg/hr) increased fractional sodium excretion 46-fold in compensated rats, but only 18-fold in decompensated rats. A similar pattern of responsiveness to ANF was observed in urinary cyclic GMP excretion. Chronic losartan treatment restored the natriuretic and urinary cyclic GMP excretion responses of decompensated rats to ANF. The improvement in the natriuretic response after losartan treatment was associated with a suppression of the previously elevated plasma aldosterone. These results demonstrate the pivotal role of angiotensin II in the development of sodium retention and of the blunted renal response to ANF in CHF, and indicate why losartan is useful therapy for cardiac edema.

Angiotensin Receptor Antagonists↗
PubMed1993

Catecholamine secretion induced by tetraethylammonium from cultured bovine adrenal chromaffin cells.

The resting potential in adrenal medullary chromaffin cells is maintained by the activity of different K(+)-channels. Blockade of K(+)-channels should, at least in principle, lead to membrane depolarization, and the ensuing activation of voltage-gated Ca(2+)-channels should promote Ca2+ entry and catecholamine (CA) secretion. In support of this mechanism we found and report here that the K(+)-channel blocker tetraethylammonium (TEA) depolarized the chromaffin cell membrane, induced a substantial elevation in cytosolic [Ca2+], and a dose-dependent CA secretion reaching a maximum at 50 mM of approx. 10% of the total CA in the cells. In addition, TEA-induced CA secretion was found to be absolutely dependent on [Ca2+]o. In the presence of [Ca2+]o, TEA-stimulated CA release was blocked completely by elevated [MgCl2]o (12 mM), and inhibited in part by the Ca(2+)-channel antagonist nifedipine. The Ca(2+)-channel agonist Bay K-8644 markedly enhanced TEA-evoked CA release suggesting the involvement of L-type Ca(2+)-channels. Since, external application of TEA (30-50 mM) markedly blocked outward K+ currents but not inward currents carried by Na+ and Ca2+, we concluded that TEA stimulates CA secretion by blocking those K(+)-channels involved in the maintenance of the resting membrane potential.

Adrenal Medulla↗
PubMed1993

Plasma catecholamine, renin activity, and ACTH responses to the serotonin receptor agonist DOI in juvenile spontaneously hypertensive rats.

Mean arterial blood pressure (MAP), heart rate (HR) and arterial plasma levels of corticotropin (ACTH), renin activity (PRA) and catechols [norepinephrine (NE), epinephrine (EPI), and the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG)] at baseline and in response to the serotonin-1C/2 (5-HT1C/5-HT2) agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI, 1.0 mg/kg i.a.) in conscious, freely-moving, juvenile (4 week old) spontaneously hypertensive rats (SHR's) and age-matched Wistar-Kyoto (WKY) normotensive control rats were measured simultaneously. Baseline levels of MAP, NE, DHPG, and EPI all were significantly higher in the SHR's. There was a similar trend for PRA, but ACTH did not differ between the two strains. DOI produced marked increases in levels of MAP, ACTH, EPI, and also PRA but did not affect NE or DHPG concentrations. HR decreased only in the WKY group after administration of DOI. The magnitudes of the EPI and ACTH responses did not differ between the rat strains. Responses of MAP and PRA were significantly larger in SHR's. These results suggest that there is a selective hyperresponsiveness of PRA and blood pressure to 5-HT2 receptor stimulation parallel to a deficient baroreceptor reflex in juvenile SHR's.

Adrenocorticotropic Hormone↗
PubMed1993

Derivation of urinary dopamine from plasma dihydroxyphenylalanine in humans.

1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spill-over) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 micrograms min-1 kg-1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenyl-acetic acid. 3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 +/- (SEM) 0.01 to 0.14 +/- 0.03 nmol/min, t = 2.80, P < 0.02] and dopamine (from 1.03 +/- 0.19 to 1.30 +/- 0.28 nmol/min, t = 2.35, P < 0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Rare renal transcription of the atrial natriuretic factor gene in rats. Demonstration by polymerase chain reaction.

Renal synthesis of a peptide homologous to atrial natriuretic factor (ANF) has been demonstrated. The aim of the present study was to determine if transcription of the ANF gene occurs in the kidney. Rat renal RNA was extracted from whole kidneys, and, separately, from the cortex and outer and inner medulla of rat kidneys. Probing with rat ANF-cDNA did not reveal a detectable message in Northern blot analysis, even when large quantities of RNA were used at low stringency hybridization conditions. Therefore, reverse transcription (RT) followed by 35 cycles of polymerase chain reaction (PCR) was used to search for the renal message for ANF. Two 21-mer primers encompassing the 450 base pairs (bp) of the coding region of the gene were used. Each cycle consisted of annealing at 56 degrees C, extension at 72 degrees C, and denaturation at 94 degrees C. The PCR product was proven to be identical to the ANF gene by high stringency hybridization, which revealed the expected 450-bp hybrid band. Furthermore, the sequence of this product was identical to that of the coding region of the ANF gene. We used an RNA-specific PCR to obtain this band as a single reaction product. We conclude that the transcript of the ANF gene exists in the kidney, at extremely low levels. The low abundance of the RNA message raises major concerns about its physiologic relevance. Direct evidence for the translation of this transcript, and its quantification and localization, is still required to determine its significance.

Animals↗
PubMed1993

Urinary endothelin: a possible biological marker of renal damage.

Endothelin (ET) is a powerful vasoconstrictor peptide synthesized and secreted by the vascular endothelium. Significant amounts of ET are also produced by nonendothelial cells, mainly tubular-epithelial and mesangial cells. Large amounts of ET are found in the urine compared with the small amounts present in blood. Because most of the ET filtered from plasma is subject to degradation by neutral endopeptidase (EC 3.4.24.11) in the proximal tubule, urinary ET is probably of renal origin. The range of urinary ET excretion in healthy persons is 20 to 90 ng/day. The excretion of endothelin is modulated by several mechanical and chemical stimuli such as angiotensin II, phenylephrine, radiocontrast media, cyclosporine, and cis-platin. In addition, enhanced urinary ET excretion has been found in several forms of renal failure, both acute and chronic, and in diabetes mellitus. Thus, urinary ET has the potential of serving as a marker for renal disease.

Amino Acid Sequence↗
PubMed1993

Regulation of the urinary excretion of endothelin in the rat.

The regulation of the urinary excretion of endothelin (UETV) and its clinical significance has not yet been established. The present study was designed to examine the effect of angiotensin II (A-II), arginine vasopressin (AVP), and nifedipine on UETV. Anesthetized Munich-Wistar rats were infused with low (50 ng/kg/min) and high (500 ng/kg/min) doses of A-II for 30 min. Both doses significantly increased UETV, from nondetectable (ND) levels to 155 +/- 54 (P < .03) and 450 +/- 86 fg/min (P < .001), respectively. This effect was accompanied by a significant increase in urine flow (UV), from 6 +/- 1 to 67 +/- 12 and 89 +/- 10 microL/min, and in mean arterial pressure (MAP), from 139 +/- 4 to 187 +/- 5 and 217 +/- 3 mm Hg. Infusions of A-II with its nonspecific antagonist, saralasin, resulted in a further increase in UETV to 647 +/- 126 and 782 +/- 117 fg/min (P < .002), respectively. However, infusion of A-II with its specific antagonist, losartan, completely blocked its stimulatory effect on UETV. Infusion of AVP, 10 or 100 mU/kg/h, produced increases in MAP, from 134 +/- 3 to 165 +/- 7 and 203 +/- 4 mm Hg, and in UV from 6 +/- 1 to 37 +/- 6 and 97 +/- 17 microL/min, comparable to A-II, but AVP did not have a marked effect on UETV.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Metabolism of endothelin-1 and big endothelin-1 by recombinant neutral endopeptidase EC.3.4.24.11.

1. Inhibitors of neutral endopeptidase EC.3.4.24.11 (NEP) have been shown to attenuate the hypertensive effect of big-endothelin-1 (BET-1) in rats. To determine whether NEP converts BET-1 to endothelin-1 (ET-1), the effect of a recombinant NEP (rNEP) on BET-1 and on ET-1 was assessed in vitro. 2. Incubation of [125I]-ET-1 with 1 microgram ml-1 of rNEP resulted in degradation of the peptide within minutes. Increase in the amount of rNEP to 10 micrograms ml-1 led to total cleavage of [125I]-ET-1 within seconds. 3. Phosphoramidon (10 microM) or SQ-28,603 (100 microM) totally suppressed the degradation of [125I]-ET-1 by rNEP. 4. The degradation of [125I]-BET-1 by either 1 or 10 micrograms ml-1 of rNEP was much slower than that of [125I]-ET-1. Again, both phosphoramidon and SQ 28,603 protected the peptide from degradation. 5. Intact [125I]-ET-1 was not observed when [125I]-BET-1 was incubated with rNEP. 6. These data show that neutral endopeptidase EC.3.4.24.11 is not an endothelin converting enzyme.

Alanine↗
PubMed1993

Bradykinin does not modulate the natriuretic response to atrial natriuretic factor in rats with aortocaval fistula.

Rats with aortocaval fistula, an experimental model of congestive heart failure (CHF), display two distinct patterns of sodium excretion: some rats develop marked sodium retention and worsening edema with urinary excretion of sodium (UNaV) < 200 microEq per 24 hours, i.e., uncompensated CHF, whereas in others sodium balance rapidly returns to normal (UNaV > 1,400 microEq per 24 hours), i.e., compensated CHF. Similar patterns of sodium excretion are found in patients with CHF. The mechanisms underlying these responses are not fully understood. The present study was designed to assess whether bradykinin plays a role in the compensatory response to CHF. Infusions of either 10 or 50 micrograms/kg per minute of synthetic atrial natriuretic factor (ANF)8-33 into sham-operated control animals produced significant increases in urine flow and fractional excretion of sodium (FENa). Infusions of ANF at the same doses into rats with compensated CHF increased FENa from 0.11 +/- 0.03% to a maximum of 6.10 +/- 1.30%, whereas the rise in FENa in animals with uncompensated CHF was significantly reduced (0.05 +/- 0.01% to 0.59 +/- 0.18%) compared with sham-operated controls (0.23 +/- 0.05% to 8.32 +/- 1.0%) or the group with compensated CHF. Treatment of the compensated rats with the bradykinin antagonist HOE-140 (D-Arg,[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin) given at a rate of 100 nmol/kg per hour did not affect their renal response to the ANF. In addition, infusion of the bradykinin antagonist alone into compensated rats with aortocaval fistula had no significant effect on their basal urinary flow rate or sodium excretion during the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗