Effects of Felodipine on Microvascular Resting Tone and Responses to Nerve Stimulation and Perfusion Pressure Reduction in Rabbit Skeletal Muscle

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Abstract
The effects of felodipine, a vasoselective dihydropyridine calcium antagonist, on microvascular dynamics were investigated in skeletal muscle. The diameters of the transverse (10-28 .mu.m) and terminal (4-8 .mu.m) arterioles, located at the immediate precapillary level in the rabbit tenuissimus muscle, were registered by intravital microscopy. Topical application of felodipine (10-7-10-5 M) induced a concentration-dependent vasodilation of both arteriolar generations. The steady state response at 10-7 M revealed a relatively more pronounced dilatation of transverse (92 .+-. 30% increase in diameter) than of terminal arterioles (44 .+-. 12%). This is in contrast to muscle exercise, which elicits a more pronounced dilatation of terminal (260 .+-. 39% increase) than of transverse arterioles (103 .+-. 15%). Vasomotor nerve stimulation evoked a frequency-dependent constriction both in the absence and presence of felodipine (10-6 M). However, the vasodilatory response elicited by graded perfusion pressure reductions was eliminated by the presence of felopidine (10-7 M). Thus, the vasomotor nerve response was better preserved than the autoregulatory response in the presence of the calcium antagonist. The results indicate that felodipine dilates arterioles via an inhibition of myogenic vascular reactivity, which supports previous results obtained both in vivo and in vitro.