Arteriolar dilation mediated by capsaicin and calcitonin gene-related peptide in rats

In addition to altering vascular tone by stimulating primary afferent nerves and acting through reflex pathways, capsaicin acts locally. We examined effects of topically applied capsaicin on arteriolar diameter in striated muscle and tested the hypothesis that capsaicin can alter microvascular tone by releasing substance P (SP) or calcitonin gene-related peptide (CGRP). In anesthetized rats, the right cremaster muscle was exposed and suspended in a tissue bath filled with a physiological salt solution. Diameters of third-order arterioles were displayed and measured using in vivo video microscopy. In 17 of 20 rats, addition of capsaicin (3 x 10(-7) M) to the bath dilated arterioles (85 +/- 14% above control). Failure of a second administration of capsaicin to produce a sustained dilation in 6 of 7 arterioles that had previously dilated to capsaicin is consistent with the hypothesis that this agent causes depletion of an endogenous vasodilator. Pretreatment with an SP inhibitor did not alter capsaicin-induced dilation. CGRP (1 x 10(-10) to 2 x 10(-8) M) caused dilation similar to that caused by capsaicin. Pretreatment with a CGRP inhibitor to the bath prevented capsaicin-induced dilation, but not constriction. These results suggest that capsaicin can dilate microvessels by releasing CGRP, which can modulate tone.