Involvement of L-type calcium channels in hypoxic relaxation of vascular smooth muscle.
In the systemic vasculature, hypoxia elicits a local vasodilator response that may be partially mediated by ionic channels on vascular smooth muscle, such as adenosine triphosphate sensitive K+ channels. Recent electrophysiological studies suggest that hypoxia may also inhibit voltage-dependent Ca2+ channels (L type) on peripheral vascular smooth muscle cells. We hypothesized that hypoxia elicits relaxation of vascular smooth muscle by inhibiting L-type Ca2+ channels. In endothelium-denuded rat thoracic aortic rings contracted with phenylephrine, mild and moderate hypoxia (PO2 35 and 20 mm Hg, respectively) elicited significant relaxation. Pretreatment with the L-type Ca2+ channel antagonist nifedipine completely inhibited mild hypoxic relaxation and diminished relaxation under moderate hypoxia, whereas glibenclamide, a blocker of adenosine triphosphate sensitive potassium channels, only attenuated the response to moderate hypoxia. In rings contracted with the L-type Ca2+ channel agonist (-)BAY K 8644 both mild and moderate hypoxia elicited almost complete relaxation. Furthermore, in rings contracted with hyperkalemic solutions (85 mM K+ or 120 mM K), mild and moderate hypoxia elicited significant relaxations. Thus, we conclude that hypoxia acts directly on vascular smooth muscle to cause relaxation in part by inhibiting L-type Ca2+ channels.
Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, N. Mex., USA.
G M
GM
Herrera
B R
BR
Walker
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014665:Vasodilator Agents; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D011188:Potassium; D005905:Glyburide