Effects of gender on mitochondria‐derived middle cerebral artery function in rats (680.7)

Abstract

Significant gender differences in the composition and functionality of cerebral arteries have been shown, but effects of mitochondrial‐derived responses have not been examined. Our study tested whether mitochondrial mechanisms promoting changes in cerebral vascular tone are different in male and female rats. We examined the effects of a mitoKATP opener, diazoxide (DZ), bradykinin (BK), and sodium nitroprusside (SNP) on isolated, pressurized MCAs from 9 week old male and female Sprague‐Dawley rats. We measured levels of mitochondrial proteins of the voltage dependent anion channel (VDAC), Complex V, the fission protein DRP‐1, and endothelial and neuronal nitric oxide synthase (NOS). Levels of Complex V and VDAC were similar in male and female rats, but the protein expression of phosphorylated DRP‐1, total and phosphorylated eNOS and nNOS in MCAs were significantly higher in females than in males. However, DZ induced vasodilation was greater in male MCAs (21.1±4.5 μm to 50μM, 44.8±4.7 μm to 100 μM) compared with female MCAs (13.3±2 μm to 50 μM, 35±3.2 μm to 100 μM) whereas vasodilator responses to BK and SNP were similar for both sexes. Treatment with L‐NAME and the denudation of endothelium abolished the DZ induced vasodilation to all of the DZ concentrations in female MCAs. Our data suggest that mechanisms underlying gender differences in mitochondrial derived vasoreactivity are associated with NO production.Grant Funding Source: NIH grants HL‐077731, HL‐030260, HL‐065380, and HL‐093554.