Evidence against the role of alpha 1-adrenoceptor reserve in buffering the inhibitory effect of nifedipine on the contractility of canine vascular smooth muscle.
The relationship between the postsynaptic alpha 1-adrenoceptor reserve and the sensitivity of vasoconstriction induced by alpha-adrenoceptor agonists to the dihydropyridine Ca2+ entry blocker nifedipine was investigated in isolated muscle strips of dog mesenteric artery (DMA) and saphenous vein (DSV). The amplitudes of the contractile responses of DMA induced by phenylephrine were the same as those in DSV in the presence and in the absence of extracellular Ca2+. The use of 3 x 10(-9) M phenoxybenzamine to irreversibly block the alpha 1-adrenoceptors revealed a marked difference in the size of the alpha 1-adrenoceptor reserve between DMA (40%) and DSV (7%). In spite of a larger receptor reserve, the contractile responses induced by phenylephrine in DMA were more sensitive to nifedipine compared with those in DSV. These results suggest that the postsynaptic alpha 1-adrenoceptor reserve in vascular smooth muscle, at least in DMA and DSV, does not play an important role in buffering the inhibitory effect of nifedipine on the contractile response to a full agonist of alpha 1-adrenoceptors. Other factors, such as the difference in the membrane depolarizing effect, the ability to utilize intracellular Ca2+ for contraction, and the possible existence of alpha 1-adrenoceptor subtypes, may contribute to the different inhibitory effects of nifedipine on these blood vessels.
Guan
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YY
Department of Biomedical Sciences, McMaster University Health Sciences Centre, Hamilton, Ont., Canada.
Kwan
C Y
CY
Daniel
E E
EE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004727:Endothelium / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009543:Nifedipine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000648:ultrastructure; D013997:Time Factors
D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010656:Phenylephrine; D009543:Nifedipine; D002118:Calcium