The effects of S-nitrosocaptopril on renal filtration and blood pressure in rats.
The present investigation was performed to evaluate the effects of S-nitrosocaptopril, a novel vasodilator possessing the capacities of both an angiotensin converting enzyme inhibitor and an NO donor, on blood pressure and renal function in rats. S-nitrosocaptopril produced acute reductions in mean arterial pressure after both oral dosing (5, 10, 50 mg/kg) to chronically-catheterized awake rats and intravenous administrations (0.125, 1.25, 12.5 mg/kg) to anesthetized rats. The hypotensive magnitude and duration of S-nitrosocaptopril were dose-dependent. Acute pressure-associated reductions in the glomerular filtration rate and urine flow were observed only at high concentration of S-nitrosocaptopril (12.5 mg/kg, i.v.) in both awake and anesthetized rats. These decreases were transient, followed by an overshoot of glomerular filtration rate and urine flow above basal values. In contrast, captopril (i.v.) did not produce any significant acute effects on mean blood pressure and glomerular filtration rate in either awake or anesthetized rats. In rats with acute hypertension induced by NG-monomethyl-L-arginine (L-NMMA, 30 mg/kg, i.v.), S-nitrosocaptopril (0.125 mg/kg, i.v.) significantly abolished the hypertensive effects. In contrast, the hypertension was not affected by captopril. In two-kidney one-clipped Goldblatt hypertensive rats, oral administration of S-nitrosocaptopril (25 mg/kg, b.i.d.) for 10 days significantly reduced systolic blood pressure and preserved glomerular filtration rate. The oral antihypertensive effect of S-nitrosocaptopril was more potent than captopril (P < 0.05). In conclusion, these findings indicate that: (1) S-nitrosocaptopril provides both acute and chronic anti-hypertensive effects orally and intravenously, whereas captopril has only moderate chronic oral effects; and (2) S-nitrosocaptopril preferentially decreases blood pressure without markedly affecting glomerular filtration rate.
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Division of Nephrology-Hypertension, University of California, San Diego School of Medicine, Veterans Affairs Medical Center, 92161, USA.
Blantz
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D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000503:physiopathology; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; C060039:S-nitrosocaptopril; D002216:Captopril