Plethysmographic Evaluation of the Vascular Effects of Human Calcitonin Gene-Related Peptide in Man

Abstract

Calcitonin gene-related peptide (CGRP) is a neuropeptide with potent cardio vascular effects that include positive inotropic and chronotropic actions systemic vasodilation, and hypotension in animals and in man. The mechanism of action of CGRP is still, however, not clear, and in particular it is not known whether vasodilation by CGRP occurs by changes in cutaneous or in muscular blood flow, or both. The aim of the study was, therefore, to evaluate the cutaneous and muscular blood flow, at rest and after ischemic test, induced by an IV bolus 25 μg human CGRP infusion in 5 healthy normotensive volunteers, using a strain gauge plethysmographic procedure with venous occlusion. Human CGRP pro voked a transient but significant decrease in sistolic and diastolic blood pressure, associated with tachycardia, marked flushing, a significant increase in plasma noradrenaline, adrenaline, and cyclic AMP levels, and a slight, but significant, decrease in serum total calcium. Moreover, a significant increase in the carpal cutaneous blood flow at rest was observed, with no significant change in the lower extremity muscular blood flow at rest and after ischemic test. Finally human CGRP produced a significant increase in the venous partial 02 pressure and in the hematocrit and a significant decrease in the venous partial CO2 pressure. The results of the present study confirm the acute cardiovascular and meta bolic effects of CGRP. In fact, hypotension, tachycardia, flushing, and the increased cutaneous blood flow indicate a systemic vasodilation by the neuropep tide, with a secondary sympathetic response, as documented by the augmented catecholamine and cyclic AMP plasma levels. Moreover, the plethysmographic study suggests a blood flow redistribution, from the muscular tissues to the cutaneous surface, with a relative lower oxygen uptake and CO2 release and a partial hemoconcentration phenomenon. In conclusion, these results are in agreement with the hypothesis that the vasodilative action of human CGRP is stronger on the skin than on the muscles of the lower extremities, even if a concomitant involvement of other vascular beds such as the splanchnic territory, by CGRP, cannot be excluded.