Endothelium-dependent hyperpolarization of smooth muscle cells in rabbit femoral arteries is not mediated by EDRF (nitric oxide).
Acetylcholine elicits an endothelium-dependent hyperpolarization of vascular smooth muscle cells. The experiments reported here tested the hypothesis that this hyperpolarization is mediated by the endothelium-derived relaxant factor (EDRF) identified as nitric oxide. Membrane potential was recorded with standard glass microelectrodes in smooth muscle cells in segments of rabbit femoral arteries. In endothelium-intact vessels, smooth muscle cells (resting potential: -67.0 +/- 1.3 mV) hyperpolarized significantly (P less than 0.001) by 5.7 +/- 0.9 mV in response to acetylcholine (1 microM). Inhibition of EDRF, either in the presence of hemoglobin or by pretreatment with gossypol, attenuated the relaxation elicited by acetylcholine in endothelium-intact segments precontracted with 0.1 microM noradrenaline but had no significant effect on either the control membrane potential (-62.2 +/- 1.9 mV and -68.5 +/- 2.1 mV, respectively) or the hyperpolarization in response to acetylcholine (5.0 +/- 1.6 mV and 5.8 +/- 1.6 mV, respectively). In contrast, in vessel segments with the endothelium removed, the hyperpolarization in response to acetylcholine was abolished although the control membrane potential (-68.0 +/- 5.1 mV) was not significantly different from that in endothelium-intact vessels. Sodium nitroprusside, an endothelium-dependent vasodilator and exogenous analog of EDRF, also had no significant effect on membrane potential. The lack of response to acetylcholine was not merely the result of nonspecific damage to the smooth muscle cells: vessel segments without endothelium were still able to hyperpolarize in response to various other vasodilators. These results suggest that the endothelium-dependent hyperpolarization of vascular smooth muscle cells in response to acetylcholine is not mediated by EDRF.
Huang
A H
AH
Institut für Angewandte Physiologie, Universität Freiburg, Federal Republic of Germany.
Busse
R
R
Bassenge
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006454:Hemoglobins / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits
D001685:Biological Factors; D006454:Hemoglobins; D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine