Effects of calcitonin gene-related peptide on vascular resistance in rats:role of sex steroids

Effects of calcitonin gene-related peptide on vascular resistance in rats: role of sex steroids. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H2063- H2068, 1999.-It has been demonstrated in reflex-intact animals that the sen sitivity to calcitonin gene-related peptide (CGRP) is increased during preg nancy and that this action is mediated by sex steroids but not by nitric ox ide (NO). We assessed the effects of CGRP in the following groups of anesth etized ganglion-blocked rats: 1) pregnant, 2) ovariectomized, and 3) ovarie ctomized and treated with estradiol and progesterone. Changes in mean arter ial pressure (MAP) were assessed after the administration of varying doses of CGRP. Decreases in MAP after CGRP administration were significantly grea ter in pregnant rats and ovariectomized rats administered sex steroids than in ovariectomized controls. The CGRP antagonist CGRP(8-37) produced a pres ser response of similar magnitude in both pregnant and ovariectomized rats. We also assessed the effects of CGRP and the modulating role of NO in the isolated uterine vascular bed preparation. CGRP reduced perfusion pressure to a greater degree in ovariectomized animals treated with sex steroids tha n in ovariectomized animals. This response was attenuated by pretreatment w ith an NO synthesis inhibitor. CGRP(8-37) produced a similar increase in pe rfusion pressure in both groups. We conclude that I) the increased vascular sensitivity observed during pregnancy or after treatment with sex steroids is in part mediated by NO, and 2) CGRP(8-37) has a vasoconstrictor action of its own.