Effects of chronic NO synthase inhibition in rats on renin-angiotensin system and sympathetic nervous system.
This study was designed to assess the role of renin and of the sympathoadrenal system in the maintenance of the hypertension induced by chronic nitric oxide synthase (NOS) inhibition in rats kept on a normal (RS) or a low-sodium (LS) diet. With the administration of NG-nitro-L-arginine methyl ester (L-NAME) in drinking water (0.4 milligrams) for 6 wk, mean intra-arterial blood pressure rose to a similar extent to 201 mmHg in the RS and 184 mmHg in the LS animals. Simultaneously, plasma norepinephrine was increased to 838 and 527 pg/ml and epinephrine to 2,041 and 1,341 pg/ml in RS and LS, respectively. Plasma neuropeptide Y levels did not change. Plasma renin activity rose to 21 ng.ml-1.h-1 in RS but remained at 44 ng.ml-1.h-1 in the LS. Both losartan (10 mg/kg) and phentolamine (0.1 mg/kg) intravenous bolus injections reduced blood pressure considerably in the L-NAME hypertensive animals. Whole brain NOS activity was reduced by 84%. Hypertension induced by chronic NOS inhibition in LS as well as in RS fed rats seems to be sustained by an interaction of several mechanisms, including the activation of the sympathetic nervous system and the renin-angiotensin system.
Zanchi
A
A
Hypertension Division, University Hospital, Lausanne, Switzerland.
Schaad
N C
NC
Osterheld
M C
MC
Grouzmann
E
E
Nussberger
J
J
Brunner
H R
HR
Waeber
B
B
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000201:enzymology*; D003404:Creatinine / Q000097:blood; D004039:Diet, Sodium-Restricted; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009478:Neuropeptide Y / Q000097:blood; D019001:Nitric Oxide Synthase; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D009478:Neuropeptide Y; D013777:Tetrazoles; D001120:Arginine; D003404:Creatinine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D012083:Renin; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine