Enhanced circulating levels of neurally derived calcitonin gene related peptide in spontaneously hypertensive rats.
OBJECTIVE
Calcitonin gene related peptide (CGRP) is a potent endogenous vasodilator. The peptide is released from perivascular nerve endings and can normally be detected in the circulation. An attempt was made to determine the concentrations and partially characterise the immunoreactive forms of circulating CGRP in a genetically hypertensive rat strain, the "spontaneously hypertensive rat" (SHR) and its genetic control, Wistar-Kyoto (WKY).


METHODS
Immunoreactive plasma CGRP levels were measured using a highly sensitive carboxyl terminal specific CGRP radioimmunoassay together with high performance liquid chromatography. Plasma immunoreactive CGRP (i-CGRP) levels were also measured 6 h after intraperitoneal colchicine administration (10 mg.kg-1 body weight) to both groups of rats.


METHODS
Eight SHR rats were compared with eight WKY rats, both groups aged 7 weeks.


RESULTS
Mean i-CGRP levels were threefold higher in the SHR group compared to controls, while plasma calcitonin levels were not different between the two groups. There was a significant correlation (Kendall's correlation coefficient, r = 0.57; p = 0.024) between i-CGRP levels and the mean systolic blood pressure (measured by the indirect tail cuff method) in SHR but not WKY rats. Similar profiles of i-CGRP were observed in both SHR and WKY rats, when acid-methanol extracts of pooled plasma were chromatographed under similar conditions. It was also confirmed that circulating CGRP in both SHR and WKY strains was derived from perivascular nerve endings, by demonstrating a complete abolition from plasma of previously detectable i-CGRP following the administration of colchicine.


CONCLUSIONS
The study shows that CGRP is normally released from vascular nerve endings, and that high concentrations of the circulating peptide are found in hypertension. This might represent a mechanism to counteract the excessive vasoconstrictor influences that underly the development and maintenance of hypertension.
Zaidi
M
M
Department of Cellular and Molecular Sciences, St George's Hospital Medical School, London, United Kingdom.
Bevis
P J
PJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D003078:Colchicine / Q000494:pharmacology; D006973:Hypertension / Q000097:blood*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D015740:Calcitonin Gene-Related Peptide; D003078:Colchicine