Effect of ouabain on adenosine receptor-mediated hyperpolarization in porcine coronary artery smooth muscle.
We investigated the effect of inhibitors of endothelium-derived nitric oxide and sodium-potassium (Na(+)-K+) pumps on adenosine receptor-mediated hyperpolarization of porcine coronary artery smooth muscle with and without endothelium. The average resting membrane potential (RMP) in porcine coronary artery smooth muscle was -51.5 +/- 0.2 and -50.7 +/- 0.2 mV, in the presence and absence of endothelium, respectively. Neither ouabain, N-nitro-L-arginine methyl ester (L-NAME) nor ouabain and L-NAME in combination significantly affected the resting membrane potential in the absence of vasodilator agonists. Adenosine agonists, 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine at 10(-5) M caused a significant increase in RMP with intact endothelium and caused a smaller but significant increase in RMP in the absence of endothelium. Ouabain (10(-5) M) in the absence of L-NAME significantly reduced hyperpolarization due to 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine in the presence of endothelium. However, in the absence of endothelium, its inhibitory effect was not significant. When ouabain plus L-NAME (10(-5) M) were given simultaneously, the hyperpolarization caused by adenosine agonists was significantly further attenuated nearly to the RMP level. Attenuation of the response to 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine by ouabain was not reversed by the nitric oxide precursor, L-arginine (10(-5) M) both in the presence and absence of endothelium. These results suggest that hyperpolarization of vascular smooth muscle of the porcine coronary artery by adenosine agonists is at least partly endothelium dependent and possibly involves the Na(+)-K+ pump and the release of nitric oxide.
Olanrewaju
H A
HA
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Hargittai
P T
PT
Lieberman
E M
EM
Mustafa
S J
SJ
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000502:physiology; D013552:Swine
D018047:Receptors, Purinergic P1; D010042:Ouabain