Renal and systemic effects of urodilatin in rats with high-output heart failure.
Urodilatin is a recently discovered natriuretic peptide [ANP-(95-126)] of renal origin, with a primary structure similar to ANP-(99-126). However, urodilatin is not biologically inactivated by renal endopeptidase, and it is a more potent natriuretic agent than ANP-(99-126). The present study was carried out to investigate the renal and systemic effects of urodilatin in rats before and after the induction of congestive heart failure (CHF) by creation of an aortocaval fistula (ACF). Administration of urodilatin in incremental doses (0.75-12 micrograms.kg-1.h-1) to Inactin-anesthetized sham-operated control rats resulted in dose-dependent increases in urine flow, glomerular filtration rate (GFR), excretion of guanosine 3',5'-cyclic monophosphate (cGMP), sodium, and potassium, and a significant decrease in mean arterial blood pressure. In rats with ACF the baseline values for GFR and sodium excretion were significantly lower than in control rats. Urodilatin infusion in rats with ACF led to significant increases in urine flow and sodium excretion, but the absolute levels of diuresis and natriuresis were significantly lower in rats with CHF than in normal rats. When urodilatin was infused into rats with ACF pretreated with neutral endopeptidase inhibitor (NEP-I; SQ-28,063 at a dose of 40 mg/kg iv), the absolute urine flow and sodium excretion were not different from that obtained in control rats. Thus the attenuated natriuretic and diuretic response to ANP-(99-126) in heart failure was not observed with urodilatin.(ABSTRACT TRUNCATED AT 250 WORDS)
Abassi
Z A
ZA
Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Powell
J R
JR
Golomb
E
E
Keiser
H R
HR
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002302:Cardiac Output; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006333:Heart Failure / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D015260:Neprilysin / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004232:Diuretics; D004338:Drug Combinations; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D015260:Neprilysin