Endothelial potentiation of relaxation response to ascorbic acid in rat and guinea pig thoracic aorta.
The role of the endothelium was evaluated in the relaxation of rat and guinea pig aortic rings induced by ascorbic acid. Ascorbic acid relaxed rat and guinea pig aortic rings that were previously contracted with submaximal dose of phenylephrine (PE), in a concentration dependent manner. Removal of the endothelium significantly reduced the sensitivity but not the magnitude of the response to ascorbic acid. Methylene blue, but not propranolol, blocked the endothelial augmentation of vascular relaxation to ascorbic acid. Vessels precontracted with potassium chloride (high K+) were also relaxed by ascorbic acid. Methylene blue also inhibited the response to ascorbic acid in the intact vessels precontracted with high K+. A23187 and acetylcholine, but not ADP, variably caused endothelium dependent component relaxation in guinea pigs, whereas all of these three probes constantly caused it. In Ca(2+)-free medium, Ca(2+)-induced contraction of high K(+)-depolarized rat aorta was inhibited by the presence of ascorbate, which was more pronounced in endothelium intact rings than in endothelium denuded ones. PE-induced contraction in the presence of different concentrations of ascorbate reduced both the sensitivity and the maximal contractile force in rat aorta. Ascorbic acid (0.125-32 mM) did not change the pH in the medium. From these findings, it is speculated that 1) receptor- and potential-operated Ca2+ channels may be modulated by ascorbate, 2) endothelium has a significant role in promoting relaxation induced by ascorbic acid.
Chang
K C
KC
Department of Pharmacology, College of Medicine, Gyeongsang National University, Chinju, Korea.
Chong
W S
WS
Sohn
D R
DR
Kwon
B H
BH
Lee
I J
IJ
Kim
C Y
CY
Yang
J S
JS
Joo
J I
JI
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001205:Ascorbic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D001205:Ascorbic Acid