Enhancement of endothelium-dependent relaxation in the aorta from stroke-prone spontaneously hypertensive rats at developmental stages of hypertension.
1. Endothelium-dependent relaxation (EDR) in aortic rings from young (8 weeks) and adult (16 weeks and 20 weeks) stroke-prone spontaneously hypertensive rats (SHRSP) was investigated in comparison with age-matched Wistar-Kyoto rats (WKY). 2. At 8 weeks, acetylcholine (3 x 10(-9)-10(-5) mol/L) and ionomycin (4 x 10(-8)-10(-6) mol/L)-induced EDR in SHRSP aortae was significantly enhanced compared to that in WKY aortae. Mechanical denudation of the endothelium completely abolished, and pretreatment of aortae with NG-monomethyl L-arginine (1 mmol/L), an inhibitor of nitric oxide formation, greatly reduced the relaxation in both strains. Indomethacin (10(-5) mol/L), a cyclo-oxygenase inhibitor that blocks the production of endothelium-derived contracting factors, did not significantly alter the relaxation by acetylcholine at this age. There was no difference in endothelium-independent relaxation of denuded aortae by sodium nitroprusside (10(-9)-10(-6) mol/L) and 8-bromoguanosine 3', 5'-cyclic monophosphate (10(-6)-10(-3) mol/L). 3. In adult SHRSP with established hypertension, however, the acetylcholine (10(-8)-10(-5) mol/L)-induced relaxation markedly diminished at any of the concentrations tested compared to that observed in 8 weeks old SHRSP and WKY at 8-20 weeks of age. This finding differed from other observations where the relaxation in SHRSP was impaired only at higher concentrations of acetylcholine. Indomethacin pretreatment of aortae from 20 week old SHRSP restored acetylcholine-induced EDR to a level comparable with that in age-matched WKY.(ABSTRACT TRUNCATED AT 250 WORDS)
Onda
T
T
University of Shizuoka, School of Pharmaceutical Sciences, Japan.
Mashiko
S
S
Hamano
M
M
Tomita
I
I
Tomita
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000254:growth & development*; D017208:Rats, Wistar
D016232:Endothelins; D009569:Nitric Oxide; D000109:Acetylcholine; D007213:Indomethacin