Bay K 8644, a dihydropyridine calcium agonist, augments vasoconstrictor responses to endogenous and exogenous noradrenaline in the peripheral vasculature of the dog

Abstract

The effect of Bay K 8644 (a substance known to increase calcium influx through the voltage-dependent calcium channel) on vasoconstrictor responses of resistance vessels to endogenous and exogenous noradrenaline (NA) was investigated in pentobarbitone-anaesthetized dogs which had also undergone spinal anaesthesia and bilateral vagotomy and received atropine. In these dogs the saphenous arterial bed was perfused at fixed flow rates with autologous blood to give perfusion pressure close to the systemic blood pressure. Electrical stimulation (3-30 Hz) of the saphenous nerve and single intra-arterial (i.a.) injections of noradrenaline (NA, 0.03-3 micrograms) produced an increase in perfusion pressure (vasoconstriction) in a frequency- and a dose-dependent manner, respectively. Intra-arterial infusions of Bay K 8644 (3 and 10 micrograms min-1) per se produced no significant change in perfusion pressure. However, these infusions augmented vasoconstrictor responses to both saphenous nerve stimulation (endogenous NA) and i.a. NA (exogenous NA). These results suggest that augmentation by Bay K 8644 of vasoconstrictor responses of resistance vessels to endogenous and exogenous NA is probably due to promotion of the calcium influx through calcium channels closely associated with alpha-adrenoceptors in smooth muscle cells there.