Pregnancy and steroid hormones enhance the systemic and regional hemodynamic effects of calcitonin gene-related peptide in rats

Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide known to be involved in the regulation of vascular resistance. Several lin es of evidence suggest that CGRP plays a role in the vascular adaptations t hat occur during normal pregnancy; however, the effects of exogenous CGRP o n systemic and regional hemodynamics during pregnancy remain unknown. There fore, the purpose of this study was to determine the hemodynamic effects of systemically administered CGRP in adult pregnant (Day 19) and ovariectomiz ed (ovx) rats using the radioactive microsphere technique. In addition, we also used ovariectomized rats treated for 3 days with estradiol (E-2), prog esterone (P-4), E-2 + P-4 in sesame oil, or oil only to assess if these hor mones regulate the CGRP-induced hemodynamic changes. On the day of study, c atheters were inserted into the left cardiac ventricle (through the right c arotid artery), right jugular vein, and caudal tail artery. Hemodynamic stu dies using radioactive microspheres were then performed in conscious rats 3 h after recovery from anesthesia. Blood pressure and heart rate were conti nuously monitored, and left ventricular pressure was determined immediately prior to each microsphere injection. Microspheres labeled with either Ce-1 41 or Sr-85 were injected prior to and 2 min following the i.v. bolus injec tion of CORP (270 pmol/kg body weight [BW]). Mean arterial pressure (MAP) a nd total vascular resistance in pregnant rats was lower than in ovx rats, a nd this was further decreased with an i.v. bolus injection of 270 pmol CGRP /kg BW. Cardiac output was elevated with further increases upon CGRP admini stration in pregnant but not in ovx rats. The CGRP-induced changes in MAP, total vascular resistance, and cardiac output in E-2 + P-4-treated rats wer e similar to that observed in Day 19 pregnant rats, indicating that CGRP ef fects on these parameters during pregnancy may be modulated by steroid horm ones. Both pregnancy and E-2 + P-4 treatment in ovx rats caused significant decreases in CGRP-induced resistance in mesenteric, coronary, and renal va sculature. Thus, the vasodilatory sensitivity to CGRP during pregnancy may be mediated through decreased total vascular resistance, particularly to co ronary, mesenteric, and renal vascular beds. Thus, CGRP-induced vasodilator y effects may play a role in mediating vascular adaptations that occur duri ng pregnancy and that steroid hormones may modulate these CGRP effects.