Effects of felodipine on local and neurogenic control of vascular resistance.
Arterial vascular resistance is established by myogenic mechanisms and is modulated both by local factors such as vasodilator metabolites and by remote controls of neurogenic and hormonal origin. This paper reports on the effects of felodipine and hydralazine on the myogenic tone and the neurogenic control of the vascular resistance of skeletal muscle. The vascular bed of the calf muscle of anesthetized cats was isolated and autoperfused at a constant flow. The sympathetic vasomotor nerves were activated by efferent stimulation of the lumbar sympathetic chain. Intraarterial infusion of felodipine and hydralazine reduced, in a dose-dependent manner, basal vascular resistance determined by myogenic factors and the vasoconstriction induced by nerve stimulation. After the infusion of felodipine, the vasoconstrictor responses to low, physiological rates of stimulation (0.5-4 Hz) were depressed to the same relative extent as resistance determined by myogenic factors, whereas the vasoconstrictor responses to supramaximal stimulation rates (16-32 Hz) were relatively more resistant. Felodipine had no effect on noradrenaline (NA) release during vasomotor nerve stimulation as determined by the NA venoarterial concentration difference. Hydralazine also reduced basal vascular resistance in a dose-dependent manner, but in contrast to felodipine, supramaximal doses of hydralazine totally abolished vasoconstrictor responses to supramaximal stimulation rates (32 Hz). It is concluded that felodipine reduces vascular resistance by a direct action on the contraction of vascular smooth muscle in the resistance vessels, as myogenic activity and physiological levels of neurogenic vasoconstriction are equally suppressed by felodipine. During supramaximal stimulation of vasomotor nerves, a separate activation pathway or more proximal vascular segments are likely to be engaged that are less sensitive to felodipine.
D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D015736:Felodipine; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009568:Nitrendipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects*; D014666:Vasomotor System / Q000502:physiology
D009568:Nitrendipine; D015736:Felodipine; D009638:Norepinephrine