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

Yan Liu, Takuya Tsuchihashi, Shuntaro Kagiyama, Kiyoshi Matsumura, Isao Abe, Masatoshi Fujishima

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

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 N(G)-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 α-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.

Original languageEnglish
Pages (from-to)1165-1173
Number of pages9
JournalJournal of hypertension
Volume16
Issue number8
Publication statusPublished - 1998

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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