Effects of calcitonin gene-related peptide on vascular resistance in rats: role of sex steroids.
It has been demonstrated in reflex-intact animals that the sensitivity to calcitonin gene-related peptide (CGRP) is increased during pregnancy and that this action is mediated by sex steroids but not by nitric oxide (NO). We assessed the effects of CGRP in the following groups of anesthetized ganglion-blocked rats: 1) pregnant, 2) ovariectomized, and 3) ovariectomized and treated with estradiol and progesterone. Changes in mean arterial pressure (MAP) were assessed after the administration of varying doses of CGRP. Decreases in MAP after CGRP administration were significantly greater in pregnant rats and ovariectomized rats administered sex steroids than in ovariectomized controls. The CGRP antagonist CGRP8-37 produced a pressor 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 than in ovariectomized animals. This response was attenuated by pretreatment with an NO synthesis inhibitor. CGRP8-37 produced a similar increase in perfusion pressure in both groups. We conclude that 1) the increased vascular sensitivity observed during pregnancy or after treatment with sex steroids is in part mediated by NO, and 2) CGRP8-37 has a vasoconstrictor action of its own.
Grewal
M
M
Department of Obstetrics and Gynecology, University of California, Los Angeles, California 90095, USA.
Cuevas
J
J
Chaudhuri
G
G
Nathan
L
L
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D009569:Nitric Oxide / Q000502:physiology; D010052:Ovariectomy; D010446:Peptide Fragments / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000098:blood supply; D014655:Vascular Resistance / Q000187:drug effects*
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D009569:Nitric Oxide; D011374:Progesterone; D004958:Estradiol; D015740:Calcitonin Gene-Related Peptide