Calcitonin Gene-Related Peptide Relations to the Arterial Hypertension in Spontaneously Hypertensive Rats

Abstract

Calcitonin gene-related peptide (CGRP) is localized in C and Aδsensory fibers and associated with innervation of smooth muscles inthe heart and vasculature. There are two mechanisms that CGRP participatesin regulating cardiovascular events. 1) Locally, CRPP is released to increase blood flow in the skin: vasodilation plays a role in regulating inflammation and enhances wound healing. 2) Systemically,CGRP, in animal studies, demonstrates that cardiovascular disease like hypertension can be reduced due to its vasodilator activity.However, the mechanism regarding when and how it is released is not fully understood.Transverse cryosections of ventricles of Spontaneously Hypertensive rats (SHR, n=3) and Wistar Kyoto rats (WKY, n=3) were examined.All animals were male and one-year-old. First, neural structures were stained immunohistochemically for protein gene product 9.5(PGP 9.5 – general neuronal marker) and CGRP. Then, nerve fractions stained by PGP 9.5 and CGRP were measured using the thre shold function and expressed as percentages from the total nerve cross-section area. Results were described as mean ± standard error and compared by Student t-test, p-value<0.05.The most prominent intrinsic nerves occurred within the epicardium and on the surface level of the myocardium. The rest of the myocardium and endocardium contained only a mesh work of nerve fibers. Epicardiac nerves were arranged similarly on both right and left ventricles. The nerves cross-sections appeared in various sizes, although on average were comparable in both groups (WKY 611±50 vs.SHR 797±118 μm2, p=0.152). Nevertheless, the area fraction stainedwith PGP9.5 was more significant in the normotensive group (WKY75±1.5% vs. SHR 69±0.8%, p<0.000). On the other hand, the CGRParea fraction significantly (almost twice) decreased in the hypertensive group, probably due to lowered vasodilative activity (WKY 9.9±0.7vs. SHR 5.4±0.2, p<0.000).Due to the potent vasodilating effects, there are changes in themyocardial tissue CGRP in the hypertensive group compared to the normotensive group. This study was supported by Grant No. S-MIP-19-23 from the Research Council of Lithuania.