Accelerated senescence of endothelial progenitor cells in hypertension is related to the reduction of calcitonin gene-related peptide

Objectives To explore whether the accelerated senescence of endothelial progenitor cells (EPCs) is related to the reduction of calcitonin gene-related peptide (CGRP) in hypertension. Methods and results In-vivo studies, plasma levels of CGRP and the number of senescent EPCs were measured in hypertensive humans and animals, from which the EPCs were isolated to examine the production of CGRP. Moreover, rutaecarpine, as an agent or tool to stimulate CGRP production, was used in hypertensive animals. The effects of rutaecarpine on angiotensin II-induced EPCs senescence were evaluated in vitro. The results showed that the number of circulating senescent EPCs was significantly increased in hypertension concomitantly with the decreased plasma level of CGRP and the decreased CGRP mRNA expression in EPCs. Administration of rutaecarpine reversed EPC senescence along with an elevation in CGRP production in spontaneously hypertensive rats. In the angiotensin II-induced EPCs senescence, the CGRP mRNA expression was reduced, which was reversed by rutaecarpine. The effect of rutaecarpine on EPCs was canceled in the presence of capsazepine, a selective antagonist of transient receptor potential vanilloid 1. Conclusion The results suggest that CGRP may work as an endogenous protective substance to counteract EPCs senescence in hypertension and the accelerated EPCs senescence in hypertension was related to the reduction of CGRP. J Hypertens 28:931-939 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.