NG-monomethyl-L-arginine-induced pressor response at developmental and established stages in spontaneously hypertensive rats.
The effect of nitric oxide (NO) pathway inhibitor, NG-monomethyl-L- arginine (L-NMMA), on arterial blood pressure was examined in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs) to investigate whether the vasodilating effect of basal levels of NO, one of the endothelium-derived relaxing factors, is preserved during the development of hypertension. L-NMMA (1-100 mg/kg i.v.) produced dose-dependent increase in arterial pressure and bradycardia in anesthetized and conscious SHRs and WKYs. L-Arginine, a precursor of NO, inhibited the pressor response to L-NMMA. The L-NMMA-induced increases in arterial pressure in both 5- to 6- and 12- to 13-week (wk)-old anesthetized SHRs were similar to those of age-matched WKY controls; rather, the increase was significantly larger in 53- to 54-wk-old SHRs than in the age-matched WKYs. In conscious SHRs (13-14 wk-old), L-NMMA induced larger hypertensive effect than in the age-matched WKYs. The amplitude of acetylcholine (ACh)-induced hypotension was somewhat larger in 5- to 6- and 12- to 13-wk-old anesthetized SHRs compared with the age-matched WKY controls. The duration of the hypotension in 5- to 6- and 12- to 13-wk-old anesthetized SHRs was similar to the age-matched WKY controls. L-NMMA significantly reduced the duration of the ACh-induced hypotension; an effect which was recovered by L-arginine. However, L-NMMA did not decrease the amplitude of the hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
J
J
Yamazaki
N
N
Fujita
T
T
Nagao
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D001120:Arginine; D000109:Acetylcholine