This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Supowit, S. C. Articles by DiPette, D. J. Search for Related Content PubMed PubMed Citation Articles by Supowit, S. C. Articles by DiPette, D. J. Related Collections Other hypertension

(Hypertension. 2001;37:728.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Nerve Growth Factor Enhances Calcitonin Gene-Related Peptide Expression in the Spontaneously Hypertensive Rat

Scott C. Supowit; Huawei Zhao; Donald J. DiPette

From the Michigan State University, College of Human Medicine, Department of Medicine, East Lansing, Michigan.

Correspondence to Scott C. Supowit, PhD, Michigan State University, B-338 Clinical Center, East Lansing, MI. E-mail scott.supowit{at}ht.msu.edu

Calcitonin gene–related peptide (CGRP) expression is markedly reduced in dorsal root ganglia neurons in the spontaneously hypertensive rat (SHR). This decrease in such a potent vasodilator may contribute to the elevated blood pressure. Therefore, the purpose of this study was to determine whether stimulation of neuronal CGRP expression in SHR, by means of the administration of nerve growth factor, would lower the blood pressure. Nerve growth factor (10 nmol/L per kg/d, IP) was given to 12-week SHR (n=8 to 11/group) once a day for 1, 3, and 7 days. Control SHR received vehicle only. All rats were instrumented for CGRP receptor antagonist (CGRP_8–37) administration (intravenous) and mean arterial pressure recording. Both the 1- and 3-day NGF treatments lowered the mean arterial pressure to 147±5 and 147±3 mm Hg, respectively, compared with controls (166±3 mm Hg). However, by day 7, the mean arterial pressure had returned to control levels (169±5 mm Hg). CGRP_8–37 administration produced a significant mean arterial pressure increase in all 3 nerve growth factor–treated groups (14±2, 10±2, and 13±2 mm Hg). CGRP mRNA levels in dorsal root ganglia were increased in the 3 neurotrophin-treated groups, whereas CGRP peptide content was higher at days 3 and 7. Therefore, nerve growth factor treatment of SHR can enhance neuronal CGRP expression. At days 1 and 3, nerve growth factor produces a depressor response that is primarily mediated by CGRP as evidenced by the pressor effect of CGRP_8–37. At day 7, CGRP also plays a counterregulatory role, even though the mean arterial pressure has returned to control levels. This finding may result from a nerve growth factor–mediated upregulation of a pressor system that counteracts the hypotensive actions of CGRP. Thus, these data suggest that the decreased production of CGRP in SHR could contribute to the hypertension.

Key Words: calcitonin gene–related peptide • rat, spontaneously hypertensive • blood pressure • nerve growth factor • RNA

This article has been cited by other articles:

				S. C. Supowit, R. T. Ethridge, H. Zhao, K. A. Katki, and D. J. DiPette Calcitonin gene-related peptide and substance P contribute to reduced blood pressure in sympathectomized rats Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1169 - H1175. [Abstract] [Full Text] [PDF]

				S. D. Brain and A. D. Grant Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin Physiol Rev, July 1, 2004; 84(3): 903 - 934. [Abstract] [Full Text] [PDF]

				P. L. Durham and A. F. Russo Stimulation of the Calcitonin Gene-Related Peptide Enhancer by Mitogen-Activated Protein Kinases and Repression by an Antimigraine Drug in Trigeminal Ganglia Neurons J. Neurosci., February 1, 2003; 23(3): 807 - 815. [Abstract] [Full Text] [PDF]

				K. A. Katki, S. C. Supowit, and D. J. DiPette Role Of Calcitonin Gene-Related Peptide and Substance P in Dahl-Salt Hypertension Hypertension, September 1, 2001; 38(3): 679 - 682. [Abstract] [Full Text] [PDF]