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(Hypertension. 1998;31:391.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Calcitonin Gene-Related Peptide Is a Depressor in Subtotal Nephrectomy Hypertension

Scott C. Supowit; Huawei Zhao; Diane M. Hallman; Donald J. DiPette

From the Departments of Human Biological Chemistry and Genetics (S.C.S.), and Internal Medicine (S.C.S., H.Z., D.M.H., D.J.D.). University of Texas Medical Branch, Galveston, TX 77555-1065.

Correspondence to Scott C. Supowit, PhD, University of Texas Medical Branch, 8.104 Medical Research Building, Galveston, TX 77555-1065

We previously demonstrated that the neuronal expression of calcitonin gene-related peptide (CGRP), a potent vasodilator, is increased in deoxycorticosterone-salt-induced hypertension where it acts as a compensatory vasodilator to attenuate the elevated blood pressure. To determine whether CGRP is playing a similar role in subtotal nephrectomy-salt-induced hypertension, hypertension was induced in Sprague-Dawley rats (n=6) by subtotal nephrectomy and 1.0% saline drinking water. Control rats (n=6) were sham operated and given tap water to drink. CGRP_(8–37), a CGRP receptor antagonist, was used to assess the hemodynamic role of CGRP in this setting. CGRP mRNA and peptide levels in dorsal root ganglia were also determined. Three weeks after either protocol, all rats had intravenous (for drug administration) and arterial (for continuous mean arterial pressure monitoring) catheters surgically placed and were studied in the conscious, unrestrained state. CGRP_(8–37) (3.2 or 6.4x10⁴ pmol/L in 0.1 mL saline) and vehicle were administered intravenously to all rats. Baseline mean arterial pressure was higher in the subtotal nephrectomized rats compared with the controls (173±5 versus 113±5 mm Hg, P<.001). Vehicle administration did not change mean arterial pressure in either group, and CGRP_(8–37) administration did not alter mean arterial pressure in the normotensive group. In contrast, CGRP_(8–37) administration to the subtotal nephrectomized rats rapidly increased the already elevated mean arterial pressure at both the 3.2x10⁴ pmol/L dose (7.8±1.1 mm Hg, P<.05) and the 6.4x10⁴ pmol/L dose (9.6±0.8 mm Hg, P<.01). CGRP mRNA and peptide levels in the dorsal root ganglia were not significantly different between the two groups. These data suggest that in subtotal nephrectomy-salt-induced hypertension, CGRP may play a compensatory depressor role in an attempt to lower the elevated blood pressure.

Key Words: calcitonin gene-related peptide • blood pressure • hypertension, experimental • neuropeptides • genes • RNA

Abbreviations: CGRP = calcitonin gene-related peptide • DOC = deoxycorticosterone • DRG = dorsal root ganglia • iCGRP = immunoreactive CGRP • MAP = mean arterial pressure • SN = subtotal nephrectomy

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