Activation of soluble guanylate cyclase and potassium channels contribute to relaxations to nitric oxide in smooth muscle derived from canine femoral veins.
Experiments were designed to examine mechanisms of relaxations to nitric oxide (NO) in venous smooth muscle. Rings of canine femoral veins without endothelium were suspended for measurement of isometric force in organ chambers. Concentration-response curves to NO and 8-Br-cyclic guanosine monophosphate (cGMP) were obtained in veins contracted with KCl (60 mM) or prostaglandin F2alpha (PGF2alpha; 2x10(-6) M) in the absence and presence of inhibitors of soluble or particulate guanylate cyclase or K+ channel antagonists. In rings contracted with PGF2alpha, relaxations to NO were reduced significantly by inhibition of soluble but not particulate guanylate cyclase. Relaxations to NO were reduced in rings contracted with KCI. Tetraethylammonium (10(-2) M) and glibenclamide (10(-7) M) + charybdotoxin (10(-7) M) significantly reduced relaxations to NO in rings contracted with PGF2alpha. Relaxations to 8-Br-cGMP were decreased significantly only by charybdotoxin. These results suggest that relaxations to NO in canine femoral veins involve at least two intracellular processes: activation of soluble guanylate cyclase and activation of adenosine triphosphate (ATP)-sensitive and large-conductance, Ca+2-activated K+ channels. The large-conductance, Ca+2-activated K+ channels seem to be activated by cGMP-dependent mechanisms. Therefore relaxations to NO in venous smooth muscle involve intracellular processes similar to those in arterial smooth muscle.
Bracamonte
M P
MP
Department of Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Burnett
J C
JC
Miller
V M
VM
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002463:Cell Membrane Permeability; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004789:Enzyme Activation; D005260:Female; D005268:Femoral Vein; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D001030:Apamin; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D019789:Tetraethylammonium; D006162:Guanylate Cyclase; D006152:Cyclic GMP