Estradiol-induced expression of Na+-K+-ATPase catalytic isoforms in rat arteries: gender differences in activity mediated by nitric oxide donors
We tested the hypothesis that previously demonstrated gender differences in ACh-induced vascular relaxation could involve diverse Na+-K +-ATPase functions. We determined Na+-K +-ATPase by measuring arterial ouabain-sensitive 86Rb uptake in response to ACh. We found a significant increase of Na+ pump activity only in aortic rings from female rats (control 206 ± 11 vs. 367 ± 29 nmol 86Rb/K·min-1·g wt tissue-1; P < 0.01). Ovariectomy eliminated sex differences in Na+-K+-ATPase function, and chronic in vivo hormone replacement with 17?-estradiol restored the ACh effect on Na +-K+-ATPase. Because ACh acts by enhancing production of NO, we examined whether the NO donor sodium nitroprusside (SNP) mimics the action of ACh on Na+-K+-ATPase activity. SNP increased ouabain-sensitive 86Rb uptake in denuded female arteries (control 123 ± 7 vs. 197 ± 12 nmol 86Rb/K·min -1·g wt tissue-1; P < 0.05). Methylene blue (an inhibitor of guanylate cyclase) and KT-5823 (a cGMP-dependent kinase inhibitor) blocked the stimulatory action of SNP. Exposure of female thoracic aorta to the Na+/K+ pump inhibitor ouabain significantly decreased SNP-induced and ACh-mediated relaxation of aortic rings. At the molecular level, Western blot analysis of arterial tissue revealed significant gender differences in the relative abundance of catalytic isoforms of Na +-K+-ATPase. Female-derived aortas exhibited a greater proportion of ?2-isoform (44%) compared with male-derived aortas. Furthermore, estradiol upregulated the expression of ? 2 mRNA in male arterial explants. Our results demonstrate that enhancement of ACh-induced relaxation observed in female rats may be in part explained by 1) NO-dependent increased Na+-K+-ATPase activity in female vascular tissue and 2) greater abundance of Na +-K+-ATPase ?2-isoform in females.
|Título según WOS:||Estradiol-induced expression of Na+-K+-ATPase catalytic isoforms in rat arteries: gender differences in activity mediated by nitric oxide donors|
|Título según SCOPUS:||Estradiol-induced expression of Na+-K+-ATPase catalytic isoforms in rat arteries: Gender differences in activity mediated by nitric oxide donors|
|Título de la Revista:||AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY|
|Editorial:||AMER PHYSIOLOGICAL SOC|
|Fecha de publicación:||2004|
|Página de inicio:||H1793|