PERSISTENT HYPERTENSION FOLLOWING INHIBITION OF NITRIC-OXIDE FORMATION IN THE YOUNG WISTAR RAT - ROLE OF RENIN AND VASCULAR HYPERTROPHY

Objective: To determine whether induction of arterial hypertension in young normotensive Wistar rats by chronic inhibition of nitric oxide p roduction with N(G)-nitro-L-arginine methyl ester (L-NAME) produced a form of self-sustained hypertension, and to investigate the role of th e renin-angiotensin system and vascular hypertrophy in the hypertensiv e process. Methods: Three-week-old Wistar rats were given 100 or 40 mg /kg per day L-NAME or 40 mg/kg per day L-NAME plus 100 mg/kg per day c aptopril in their drinking water for between 4 and 7 weeks. Systolic b lood pressure was measured by tail-cuff plethysmography both during tr eatment and after the treatment had been stopped. The effect of treatm ent on plasma renin was measured and the effect of treatment on mesent eric resistance artery structure was determined using a small-vessel m yograph. Results: L-NAME produced a progressive and marked increase in blood pressure during the period of treatment. Hypertension was susta ined for 14 weeks after stopping treatment. L-NAME resulted in a fourf old increase in plasma renin which remained elevated after treatment w as stopped. Blood pressure was correlated with plasma renin levels. Tr eatment with L-NAME plus captopril markedly attenuated the rise in blo od pressure and captopril also produced a marked fall in blood pressur e in rats that developed persistent hypertension. Pats with self-susta ined hypertension exhibited both cardiac and mesenteric resistance ves sel hypertrophy. The induction of vascular hypertrophy with low-dose L -NAME did not result in the development of self-sustained hypertension . Conclusions: ChroniC L-NAME treatment in young rats can produce a fo rm of persistent hypertension which is renin-dependent and which does not seem to involve a vascular amplifier mechanism.