Tissue specific susceptibility of alpha-adrenoceptor mediated vasoconstriction to nifedipine.
The influence of the calcium antagonist nifedipine on alpha 1- and alpha 2-adrenoceptor-mediated vasoconstrictor effects was investigated in vitro. Changes in tension were monitored isometrically on helical strips of canine circumflex coronary and saphenous arteries suspended in 10 ml organ baths and of saphenous arteries suspended in 10 ml organ baths and of saphenous veins superfused with Krebs-Henseleit solution. Distinction between alpha 1- and alpha 2-adrenoceptors was made by using selective alpha-adrenoceptor blocking drugs such as rauwolscine, yohimbine, corynanthine and prazosin, and the agonists noradrenaline, phenylephrine and guanfacine. In venous and both arterial vascular smooth muscles, the contractile process could be triggered by stimulation of both alpha 1- and alpha 2-like adrenoceptors. Nifedipine inhibited the venoconstrictor response to the alpha 2-agonist guanfacine, leaving that to the alpha 1-agonist phenylephrine unchanged. In saphenous arteries, nifedipine in addition to guanfacine also antagonized constrictor responses to phenylephrine, though to a significantly weaker extent. In circumflex coronary arteries, nifedipine was equally potent in antagonizing responses to both alpha 1- and alpha 2-adrenoceptor stimulation. It is suggested that the susceptibility of alpha-adrenoceptor-mediated vasoconstrictor effects to blockade by calcium antagonists depends not only on the subtype of alpha-adrenoceptor but, in addition, on the type and origin of vascular smooth muscle and may be a reflection of tissue variations in intracellular calcium stores.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine