Analysis of acetylcholine-induced relaxation of rabbit isolated middle cerebral artery: effects of inhibitors of nitric oxide synthesis, Na,K-ATPase, and ATP-sensitive K channels.
The functional importance of membrane hyperpolarization through activation of ATP-sensitive K channels, or activation of the Na,K-ATPase, was investigated for acetylcholine (ACh)-induced relaxation of the rabbit isolated middle cerebral artery (MCA) precontracted with uridine triphosphate. Incubation with glibenclamide (1 microM), a known blocker of ATP-sensitive K channels, or precontraction with a high concentration of KCl (50 mM) had no effect on ACh-induced relaxation. Similarly, inhibition of the Na,K-ATPase with ouabain (10 microM) or incubation with a potassium-free solution had either no or only a small effect on ACh-induced relaxation. In contrast, NG-nitro-L-arginine (NOLAG) (1 to 10 microM), a structural analogue of L-arginine and an inhibitor of nitric oxide synthesis, produced concentration-dependent although apparently noncompetitive inhibition of ACh-induced relaxation. This inhibition was partially reversed by application of L-arginine (100 microM), a putative precursor for nitric oxide synthesis. It is concluded that membrane hyperpolarization induced by activation of ATP-sensitive K channels or Na,K-ATPase does not play a major functional role in ACh-induced relaxation of rabbit MCA. The potent inhibitory actions of NOLAG would suggest that the major mechanism of ACh-induced relaxation is by release of nitric oxide as in other cerebral and peripheral arteries.
Parsons
A A
AA
Institute of Physiology, University of Munich, Federal Republic of Germany.
Schilling
L
L
Wahl
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014544:Uridine Triphosphate / Q000494:pharmacology
D015221:Potassium Channels; D019335:Nitroarginine; D009569:Nitric Oxide; D010042:Ouabain; D000255:Adenosine Triphosphate; D001120:Arginine; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D011188:Potassium; D005905:Glyburide; D014544:Uridine Triphosphate