Mechanisms underlying contraction and relaxation induced by nerve stimulation in monkey uterine arteries.
We investigated the mechanisms of contractile and relaxant responses to nerve stimulation by electrical pulses and nicotine in isolated monkey uterine artery strips denuded of the endothelium. In the strips contracted with prostaglandin F(2alpha), transmural electrical stimulation (5 Hz, 40 s) produced a contraction which was partially attenuated by prazosin and abolished or reversed to a relaxation by additional treatment with alpha,beta-methylene ATP. The relaxation was abolished by N(G)-nitro-L-arginine (L-NA) and restored by L-arginine but not by D-arginine. Atropine, D-NA, aminophylline and suramin, an inhibitor of P(2Y) purinoceptors, were without effect. The neurogenic relaxation was abolished by 1H-(1,2, 4)oxadiazolo(4,3)quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase. Nicotine (10(-4) mol/l) elicited contraction or relaxation of uterine arteries; the contraction was reversed by combined treatment with prazosin and alpha,beta-methylene ATP. Nicotine-induced relaxations were abolished by L-NA and restored by L-arginine. The relaxation induced by exogenously applied NO (acidified NaNO(2) solution) was not influenced by L-NA but abolished by ODQ. It is concluded that contractions induced by nerve stimulation are mediated by norepinephrine and ATP liberated from sympathetic nerves that stimulate alpha(1)-adrenoceptors and P(2x) purinoceptors, respectively. The neurogenic relaxation seems to be mediated exclusively by nitric oxide synthesized from L-arginine in perivascular nerves that activates guanylate cyclase and produces cyclic GMP in smooth muscle.
Okamura
T
T
Department of Pharmacology, Shiga University of Medical Science, Seta, Japan. okamura@belle.shiga-med.ac.jp
Ghoneim
H A
HA
Ayajiki
K
K
Ammar
E S
ES
Toda
N
N
D000255:Adenosine Triphosphate / Q000502:physiology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008251:Macaca; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D018722:Nicotinic Agonists; D019335:Nitroarginine; D009569:Nitric Oxide; D009538:Nicotine; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D011224:Prazosin