Effect of ACh on electrical and mechanical activity in guinea pig coronary arteries.
The contractile and intracellular responses to acetylcholine (ACh) were measured in isolated segments of the guinea pig circumflex coronary artery. ACh (10(-5) M) led to hyperpolarization of the membrane in the presence or absence of the H1-receptor agonist 2-(2-aminoethyl)pyridine (AEP). This hyperpolarization was associated with relaxation of vessels precontracted with AEP. Hyperpolarization and relaxation were abolished after complete removal of the endothelium. Less endothelial coverage was required to obtain a relaxation with ACh (10(-5) M) than with bradykinin (BK, 10(-7) M). BK did not initiate hyperpolarization. A23187 (10(-8) to (10(-5) M) did not relax vessels precontracted with AEP. Three muscarinic antagonists were compared and the following order of potency was obtained: atropine greater than pirenzapine greater than AFDX116. Although atropine (10(-7) M) reduced the ACh (10(-5) M)-induced hyperpolarization by 83%, this same concentration of pirenzapine had no effect on hyperpolarization. Oxyhemoglobin (10(-5) M) significantly reduced relaxation to nitroglycerine but not ACh. Methylene blue (10(-5) or 5 x 10(-5) M) inhibited relaxation to submaximal but not maximal concentrations of ACh. In vessels precontracted with elevated potassium, ACh (10(-5) M) caused contraction rather than relaxation. The onset and time to peak hyperpolarization with carbachol was more rapid with luminal as opposed to adventitial application of drug. It is concluded that relaxation and hyperpolarization with ACh in the coronary artery are mediated via the endothelium. The results are compatible with the hypothesis that relaxation is initiated by both endothelial-derived relating factor stimulation of guanylate cyclase activity and hyperpolarization of the smooth muscle.
Keef
K D
KD
Department of Physiology, University of Nevada, Reno 89557.
Bowen
S M
SM
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology / Q000379:methods; D004730:Endothelium, Vascular / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010108:Oxyhemoglobins / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D010108:Oxyhemoglobins; D002217:Carbachol; D000109:Acetylcholine; D011188:Potassium; D001920:Bradykinin