Angiotensin blockade reverses hypertension during long-term nitric oxide synthase inhibition.

• DOI: 10.1161/01.hyp.21.5.660
• Publication Date: 2012-06-12T00:24:03Z
• Authors: D M Pollock; J S Polakowski; B J Divish; T J Opgenorth
• Keywords: Male; 0301 basic medicine; Time Factors; Dose-Response Relationship, Drug; Pyridines; Angiotensin II; Nicotinic Acids; Tetrazoles; Arginine; Nitroarginine; 6. Clean water; Diuresis; Rats; 3. Good health; Rats, Sprague-Dawley; Proteinuria; 03 medical and health sciences; Hypertension; Renin; Animals; Amino Acid Oxidoreductases; Nitric Oxide Synthase

Blockade of the renin-angiotensin system was studied in male Sprague-Dawley rats during long-term inhibition nitric oxide synthase. Nitro-L-arginine-methyl ester (L-NAME) placed drinking water for 4 weeks (approximately 100 mg/kg per day). Separate groups were coadministered angiotensin II antagonist A-81988 ranging from approximately 0.001 to 1 day. Control received only tap or alone. Each week, metabolic cages, and tail-cuff blood pressures samples taken. L-NAME produced a sustained elevation pressure that completely prevented by A-81988. No changes creatinine clearance, sodium excretion, plasma concentration, urea nitrogen observed. Food intakes identical all groups. Water excretion significantly increased L-NAME-treated animals regardless additional inhibitor treatment, suggesting possible role synthase control excretion; this effect independent pressure. Although less potent than A-81988, losartan converting enzyme enalapril also blocked L-NAME-induced hypertension. In separate series experiments, not given until 2 after hypertension had fully developed rats. Within week treatment with antagonist, returned normal. We conclude these studies endogenous production produces an II-dependent form