Effect of hypertension induced by nitric oxide synthase inhibition on structure and function of resistance arteries in the rat.
To determine whether inhibition of generation of endothelium-derived relaxing factor or nitric oxide (NO) resulted in elevated blood pressure and its effect on resistance arteries, rats were offered NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase, in their drinking water. Blood pressure (BP) rose slightly from 100 +/- 2 mmHg in controls to 130 +/- 5 mmHg with 25 mg/Kg L-NAME per day and to 173 +/- 9 mmHg with 100 mg/Kg per day for 2 1/2 to 4 weeks. Rats were studied after 1-2 weeks of hypertension (BP > 150 mmHg). The concentration of cyclic guanosine monophosphate, the intracellular second messenger of NO, was significantly depressed in aorta and in the mesenteric vascular bed in L-NAME-treated rats. Mesenteric resistance arteries studied on a wire-myograph exhibited similar external and lumen diameters, whereas media width and media/lumen ratio were greater (p < 0.01). Cross-sectional area of the media was similar. Active wall tension in response to norepinephrine tended to be greater in blood vessels from L-NAME-treated rats, while responses to vasopressin and endothelin-1 were unaltered. Sensitivity to norepinephrine was significantly enhanced in L-NAME-treated rats (p < 0.001), while that to endothelin-1 and arginine8 vasopressin was similar. In conclusion, administration of an NO synthase inhibitor produces hypertension, with exaggerated media/lumen ratio in resistance arteries and enhancement of response to norepinephrine, which together with decreased NO generation may contribute to elevation of blood pressure.
Deng
L Y
LY
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Thibault
G
G
Schiffrin
E L
EL
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001158:Arteries / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance
D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases