Pregnancy and steroid hormones enhance the vasodilation responses to CGRP in rats

We recently reported that calcitonin gene-related peptide (CGRP) reversed t he hypertension induced by nitric oxide inhibition in pregnant rats and tha t this effect appeared to be progesterone dependent. In the present study, we examined whether the vasodilator responses to CGRP are increased during pregnancy and whether these responses are steroid hormone dependent. Three groups of ovariectomized (Ovx) rats (n = 4-8 rats/group) were studied 3 day s after daily treatment (subcutaneous injection) with progesterone (P; 2 mg /injection, twice daily for 3 days, in 0.2 ml of sesame oil), 17 beta-estra diol (E; 2.5 mu g/injection, twice daily for 3 days, in 0.2 mi of sesame oi l), or vehicle (sesame oil). A fourth group (n = 6 rats) of pregnant rats w as studied on day 19 of gestation. A fifth group of adult, nonpregnant rats (n = 6 rats), regardless of stage of estrous cycle, was also used in this study. Mean arterial blood pressure (MAP) was continuously monitored in ful ly awake and free-moving instrumented rats. MAP was measured before and aft er administration of either saline or varying bolus doses of CGRP (9-360 pm ol/kg body wt). CGRP produced a dose-dependent decrease in MAP in all rats with a significant (P < 0.05) reduction in MAP beginning with a CGRP dose o f 90 pmol/kg and with maximal effects observed at 360 pmol/kg. Decreases in MAP in response to CGRP were significantly (P < 0.05) greater in pregnant compared with nonpregnant rats. Similarly to pregnant rats, Ovx rats given both E and P treatments produced greater decreases in MAP in response to CG RP at 90, 180, and 360 pmol/kg doses compared with both ovary-intact and Ov x nonpregnant rats, which were not different from each other. In summary, t hese data show that 1) the hypotensive effects of CGRP are dose dependent a nd 2) the hypotensive effects of CGRP are enhanced during pregnancy and in Ovx rats treated with either E or P. Therefore, we suggest that the decreas e in vascular tone that is seen during pregnancy may be mediated, at least in part, by a sex steroid hormone-induced increase in the vascular sensitiv ity to the vasodilator effects of CGRP.