Studies on the effects of felodipine on the vascular resistance and reactivity in pentobarbital anesthetized dogs

Abstract

Bilateral perfused hindlimb preparations in pentobarbital anesthetized dogs were utilized in the present study to evaluate vasodilator effects of felodipine, in the presence and in the absence of sympathetic neurogenic tone. Vascular resistance was evaluated by establishing pressure-flow characteristics. A lower dose of this agent (0.01 mumol/kg i.v.) produced significant reductions in the systemic arterial blood pressure and vascular resistance only in the innervated but not in the denervated limb. This effect was shown to be due to interference with noradrenaline induced vasoconstriction. However, a tenfold higher dose of felodipine (0.1 mumol/kg i.v.) was indeed effective in attenuating resistance in the denervated vascular bed; this ability of the higher dose (0.1 mumol/kg) to inhibit vascular resistance may be due to an additional intracellular action of this drug affecting myogenic tone and/or due to inhibition of the vascular effects of the endogenous renin-angiotensin system. In the present experimental model, felodipine, a dihydropyridine calcium antagonist, was equally effective in inhibiting either alpha 1- or alpha 2-mediated vasoconstriction. These data suggest that the ability of felodipine to interfere with sympathetic vasoconstrictor mechanisms primarily contributes to its hypotensive effects in the barbiturate-anesthetized dogs.