Central and peripheral mechanisms involved in hypertension induced by chronic inhibition of nitric oxide synthase in rats

OBJECTIVE: To study the possible central and peripheral mechanisms involved in hypertension induced by chronic inhibition of nitric oxide synthase. METHODS: We evaluated neurohormonal and renal responses of Wistar rats to chronic oral administration of 20 and 100 mg/kg per day NG-nitro-L-arginine methyl ester (L-NAME). Effects of intracerebroventricular and intravenous injections of NO donors (NOC-18 and FK-409) and an angiotensin II type 1 receptor antagonist CV-11974, and intravenous injection of alpha-adrenergic receptor antagonist phentolamine after chronic treatment with 100 mg/kg per day L-NAME were also studied. RESULTS: The chronic treatment with L-NAME induced a sustained dose-dependent hypertension with a decrease in heart rate. Urinary levels of norepinephrine and epinephrine decreased with no changes in plasma catecholamine levels, renin activity, and vasopressin level. Serum nitrate/nitrite levels in the rats treated with the high dose of L-NAME decreased. The intracerebroventricular and intravenous injections of the NO donors reduced arterial pressure in L-NAME-treated rats to a significantly greater extent than they did that in control rats. The intravenous but not intracerebroventricular injection of CV-11974 produced a sustained decrease in arterial pressure of L-NAME-treated rats. The depressor responses to intravenous injection of phentolamine of L-NAME-treated and control rats were similar. CONCLUSIONS: Results indicate that L-NAME-induced hypertension is associated with a deficiency of nitric oxide, both peripherally and centrally. Circulating angiotensin II could contribute to the maintenance of hypertension via angiotensin II type 1 receptor while the sympathetic nervous system seems to be suppressed.