RENAL AND VASCULAR CONSEQUENCES OF THE CHRONIC NITRIC-OXIDE SYNTHASE INHIBITION - EFFECTS OF ANTIHYPERTENSIVE DRUGS

The effects of the administration of either the angiotensin converting enzyme (ACE) inhibitor, quinapril (10 mg/kg/day, orally), or the calc ium antagonist, diltiazem (100 mg/kg/day, orally), on blood pressure ( BP), renal function, and vascular reactivity in isolated perfused mese nteric beds were studied in rats treated for 8 weeks with the nitric o xide (NO) synthesis inhibitor, N-G-nitro-L-arginine methyl ester (LNAM E, 40 mg/kg/day). The oral administration of LNAME significantly incre ased systolic BP values, which reached the levels of 186 +/- 7 mm Hg a t week 8. Both quinapril and diltiazem reduced this, although the ACE inhibitor was more effective than the calcium antagonist. The chronic inhibition of NO resulted in an increase in water excretion whether or not the increase in systolic BP was prevented by the coadministration of either quinapril or diltiazem. At the end of the experiment, LNAME -treated rats presented higher proteinuria than control rats (140 +/- 4 mg/24 hours v 21 +/- 1 mg/24 hours, P < .05). This elevated protein excretion was normalized by both antihypertensive drugs. None of the t reatments was able to modify either natriuresis or plasma creatinine l evels. Endothelium-dependent relaxations to acetylcholine (10(-12) to 10(-8) mol/L) were comparable in all groups. However, the vasoconstric tion induced by either the continuous infusion of phenylephrine (10(-5 ) mol/L) or by a bolus of angiotensin II (1 nmol) was higher in the an imals that received LNAME than in control ones. The antihypertensive t herapy normalized the response to phenylephrine but not to angiotensin II. These data suggest that both quinapril and diltiazem are not only able to reduce BP elevation induced by the chronic administration of LNAME in rats, but also to prevent the renal damage and the hyperrespo nsiveness to phenylephrine induced by this NO synthesis inhibitor.