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(Hypertension. 1997;29:248.)
© 1997 American Heart Association, Inc.

Arthur C. Corcoran Memorial Lecture

Calcitonin Gene-Related Peptide Is a Depressor in N^G-Nitro-L-Arginine Methyl Ester-Induced Hypertension During Pregnancy

Pandu R. R. Gangula; Scott C. Supowit; Sunil J. Wimalawansa; Huawei Zhao; Diane M. Hallman; Donald J. DiPette; Chandrasekhar Yallampalli

From the Departments of Obstetrics and Gynecology (P.R.R.G., C.Y.), Internal Medicine (S.C.S., S.J.W., H.Z., D.M.H., D.J.D.), and Human Biological Chemistry and Genetics (S.C.S.), The University of Texas Medical Branch (Galveston).

Reprint requests to Chandra Yallampalli, DVM, PhD, Department of Obstetrics and Gynecology, 301 University Blvd, Medical Research Bldg, Rm 11.138, Galveston, TX 77555-1062. E-mail cyallamp{at}marlin.UTMB.edu

Inhibition of nitric oxide production with N^G-nitro-L-arginine methyl ester (L-NAME) increases blood pressure and fetal mortality in pregnant rats. We previously reported that administration of calcitonin gene-related peptide (CGRP) reduces the blood pressure and fetal death produced by L-NAME. To determine the hemodynamic role of endogenous CGRP in this setting, CGRP_8–37, a CGRP receptor antagonist, was used. In addition, CGRP mRNA and peptide levels were determined in dorsal root ganglia. L-NAME or control rats had intravenous (for drug administration) and arterial (for continuous mean blood pressure monitoring) catheters surgically placed and were studied in the conscious unrestrained state. Baseline blood pressure was higher in the L-NAME than the control rats on days 19, 20, and 21 or pregnancy and postpartum day 1. Vehicle administration did not change blood pressure in any group, and CGRP_8–37 (100 µg) did not change blood pressure in control groups. However, CGRP_8–37 administration to the L-NAME rats further increased blood pressure (P<.05) on days 19 (8±1), 20 (12±2), and 21 (7±1) of gestation but was without effect on postpartum day 1. Furthermore, CGRP mRNA or peptide levels in dorsal root ganglia were not different between the L-NAME and control rats at any of the time points studied. These data indicate that in experimental preeclampsia, CGRP is playing a compensatory vasodilator role to attenuate the elevated blood pressure. The mechanism of this effect appears to be an enhanced vascular responsiveness to CGRP that is attenuated after the birth of pups.

Key Words: preeclampsia • calcitonin gene-related peptide • L-NAME • gene regulation

Abbreviations: BP = blood pressure • CGRP = calcitonin gene-related peptide • DRG = dorsal root ganglia • iCGRP = immunoreactive CGRP • L-NAME = N^G-nitro-L-arginine methyl ester • MAP = mean arterial pressure • NO = nitric oxide • SHR = spontaneously hypertensive rat(s)

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