Calcitonin gene-related peptide is a depressor of deoxycorticosterone-salt hypertension in the rat.
Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide. We previously demonstrated that neuronal CGRP expression is significantly increased in deoxycorticosterone (DOC)-salt hypertensive rats. To determine the hemodynamic role of CGRP in this setting, we used CGRP8-37, a specific CGRP receptor antagonist. DOC-salt hypertension was induced in Sprague-Dawley rats. To control for DOC pellet implantation, left nephrectomy, and/or saline drinking water, we also studied four normotensive groups. Four week after the initiation of each 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. Baseline mean arterial pressure was higher in the DOC-salt than normotensive rats (175 +/- 5 versus 119 +/- 4 mm Hg, P < .001). Vehicle administration did not alter mean arterial pressure in any group, and CGRP8-37 administration (bolus doses of 3.2 x 10(4) or 6.4 x 10(4) pmol/L) did not change mean arterial pressure in the four normotensive groups. However, CGRP8-37 administration to the DOC-salt rats rapidly and significantly increased mean arterial pressure at both the lower dose (9 +/- 1 mm Hg, P < .001) and higher dose (14 +/- 1 mm Hg, P < .001). In addition, the increase in mean arterial pressure between the two CGRP8-37 doses was also significant (P < .01), indicating a dose-dependent response. We conclude that the increase in neuronal CGRP expression in DOC-salt hypertension plays a compensatory vasodilator role to attenuate the elevated blood pressure. These results provide the first conclusive evidence that CGRP plays a direct role in DOC-salt hypertension.
Supowit
S C
SC
Department of Internal Medicine, University of Texas (Galveston) Medical Branch 77555-1065, USA.
Zhao
H
H
Hallman
D M
DM
DiPette
D J
DJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002478:Cells, Cultured; D015342:DNA Probes; D003627:Data Interpretation, Statistical; D003900:Desoxycorticosterone; D006439:Hemodynamics; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D012313:RNA / Q000302:isolation & purification; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D015342:DNA Probes; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D003900:Desoxycorticosterone; D012965:Sodium Chloride; D012313:RNA; D015740:Calcitonin Gene-Related Peptide