Dehydroepiandrosterone (DHEA), a circulating steroid hormone precursor produced potent vasorelaxation in rat aorta and mesenteric arteries through blockade of L-type voltage-dependent calcium channels

Abstract

Dehydroepiandrosterone (DHEA) is known for potent cardioprotective properties and diminished DHEA level in plasma is often associated with hypertension and age-related anomalies. However, putative ex-vivo vasorelaxation potential of DHEA in systemic resistance vessels like mesenteric arteries and conduit arteries like aorta are still to be worked out. The study aimed to explore vasorelaxation potential of DHEA in superior and resistance mesenteric arteries and aorta in rats and to determine the contribution L-type Voltage dependent calcium channel (L-VDCC) in the relaxation response in these arterial tissues. Ex-vivo vasorelaxation potential of DHEA in isolated arterial tissues were evaluated and the mechanism of vasorelaxation induced by DHEA was characterized by contraction experiment in isolated arterial tissue and in-vitro calcium imaging assay using Fluo-4 in primary vascular smooth muscle cells derived from aorta. In the current study, DHEA was found to exhibit potent concentration dependent, endothelium and potassium channel independent vasorelaxation response in conduit and resistance arteries. The block of L-type VDCCs was evident from the findings that DHEA in a concentration-dependent manner inhibited both BAY K-8644 and CaCl₂-induced contractions. The results of the contraction experiment were further substantiated by Fluo-4 mediated calcium imaging assay in primary rat vascular smooth muscle wherein DHEA concentration dependently blocked noradrenaline and BAY K-8644-induced rise in intracellular calcium fluorescence. The present study showed potent endothelium and potassium channel independent vasorelaxation properties of DHEA in aorta, superior and resistance mesenteric artery mediated predominantly through blockade of L-VDCC.