title: Central and peripheral mechanisms involved in hypertension induced by chronic inhibition of nitric oxide synthase in rats.
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 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.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Tsuchihashi
authors.forename: S
authors.initials: S
authors.lastname: Kagiyama
authors.forename: K
authors.initials: K
authors.lastname: Matsumura
authors.forename: I
authors.initials: I
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Fujishima
mesh_terms: D000208:Acute Disease; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003714:Denervation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology* / Q000503:physiopathology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012849:Sinoatrial Node / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D013777:Tetrazoles; D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C081643:candesartan; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine