Nerve growth factor enhances calcitonin gene-related peptide expression in the spontaneously hypertensive rat.

Abstract

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.