Calcium-induced vasocontractions after alpha-2 adrenergic receptor activation in the dog saphenous vein: comparison to calcium-induced contractions after potassium-depolarization.
1. Calcium mediated contractile effects were evoked in phenoxybenzamine (10(-7) M)-pretreated dog saphenous vein (DSV) rings under the continuing presence of norepinephrine (3 x 10(-5) M), a condition that selectively activates alpha 2 (alpha 2)-adrenergic receptors. 2. Calcium-induced contractions in this model were dose-dependently inhibited by the alpha 2 antagonists rauwolscine and SKF-86466, while the calcium channel blockers nifedipine and verapamil produced only small non-dose related inhibitions. The receptor antagonists sulpiride, buspirone, pyrilamine and atropine showed no inhibitory effect. 3. In contrast, rauwolscine and SKF-86466 produced no inhibition of the calcium-evoked contractions in potassium-depolarized DSV rings, in which nifedipine and verapamil exhibited potent calcium antagonist activity. 4. These data provide evidence to support the presence of alpha 2 related receptor-operated calcium channels in vascular smooth muscle, which are pharmacologically distinguishable from potential-dependent calcium channels.
Lee
J Y
JY
Cardiovascular Discovery Division, Abbott Laboratories, Abbott Park, IL 60064.
Warner
R B
RB
Brune
M E
ME
DeBernardis
J F
JF
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009467:Neuromuscular Depolarizing Agents; D011942:Receptors, Adrenergic, alpha; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine