Nitroarginine-sensitive and -insensitive components of the endothelium-dependent relaxation in the guinea-pig carotid artery.
In the guinea-pig carotid arteries, nitroarginine elevated the resting tension (greater than 3 x 10(-6) M) and enhanced the noradrenaline (NA)- and high-potassium (high-K, 29.6 mM) induced contractions (greater than 10(-7) M), in a concentration-dependent manner, with no significant change in the resting membrane potential and depolarizations elicited by NA or high-K. ACh (10(-6) M) relaxed the muscles precontracted with NA or high-K by 96 or 46% of the contraction, respectively. In the presence of nitroarginine (10(-5) M) for 1-3 h, the ACh-induced relaxation was reduced to 40 or 0% of the NA- or high-K-contractions, respectively. In tissues contracted with NA and exposed to nitroarginine, the ACh-induced relaxation changed from a sustained to a transient form. ACh relaxed the muscles to a similar extent, at any given level of tension, as elevated by different concentrations of NA to 1-3 times the level produced by 10(-6) M NA, either in the presence or absence of nitroarginine. ACh (greater than 10(-8) M) produced a transient hyperpolarization of the membrane, in an endothelium-dependent manner, and the responses were blocked by atropine (10(-6) M) or high-K solution, but not by NA or nitroarginine. We propose that 1) endothelium-derived hyperpolarizing factor (EDHF) is produced by pathways independent of the biosynthesis of endothelium-derived relaxing factor (EDRF), 2) the sustained release of EDRF maintains the muscle tone at a low level, and 3) the endothelium-dependent relaxation is produced by both EDRF and EDHF, and they elicit sustained and transient relaxations, respectively.
Suzuki
H
H
Department of Physiology, Nagoya City University Medical School, Japan.
Chen
G
G
Yamamoto
Y
Y
Miwa
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine