Endothelial regulation of cyclic GMP and vascular responses in hypertension.
The mechanism whereby endothelial modulation of drug-induced vascular responses might change during hypertension was examined. Acetylcholine (ACh) (1 microM) induced maximal relaxation of aortic ring segments with intact endothelium from both Wistar-Kyoto, normotensive rats (WKY) and spontaneously hypertensive rats (SHR) at 5 to 6 weeks of age. At 15 to 18 weeks of age the relaxation response to ACh was reduced in rings from both SHR and WKY (to a greater extent in SHR) and was attenuated even more in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. The contractile responses of aortic preparations to norepinephrine (NE) (0.1 microM) were similar between 5-6-week-old and 15-18-week-old WKY, but were increased in 15-18-week-old SHR compared to 5-6-week-old SHR. Endothelial cell removal increased contractile responses to NE to a greater extent in WKY than SHR but this did not affect that seen in DOCA-salt hypertensive rats. Methylene blue treatment increased contractions of aortic rings with intact endothelium from 15-18-week-old WKY and SHR to the level detected in rubbed arteries, but it did not affect the NE-induced constriction of intact aortic rings from DOCA-salt hypertensive rats. Basal cyclic GMP concentrations in intact aortic rings were not different between SHR and WKY at 5 to 6 weeks of age. The basal aortic cyclic GMP was unchanged in WKY at 15 to 18 weeks of age, but decreased in SHR and in DOCA-salt hypertensive rats of the same age.(ABSTRACT TRUNCATED AT 250 WORDS)
Shirasaki
Y
Y
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield.
Kolm
P
P
Nickols
G A
GA
Lee
T J
TJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D003900:Desoxycorticosterone; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D003900:Desoxycorticosterone; D006152:Cyclic GMP; D000109:Acetylcholine; D009638:Norepinephrine