Na+-K+-2Cl(-) cotransporter is implicated in gender differences in the response of the rat aorta to phenylephrine

Palacios J.; Espinoza F.; Munita C.; Cifuentes F.; Michea, L.

Abstract

Inhibition of the Na +-K +-2Cl - cotransporter (NKCC1) with bumetanide reduced contractile responses to phenylephrine (PE) in male rat aortas (129 ± 4% of 60 mM KCl-induced contraction control vs 108 ± 7% bumetanide; PE 10 -5 M; P < 0.01) but did not change equivalent responses in female rat aortas. Removal of the endothelium blunted the effect of NKCC1 inhibition on the response to PE (10 -5 M) in males, whereas in denuded aorta from female rats, bumetanide reduced this response (162 ± 5% control vs 146 ± 3% bumetanide; P < 0.05). NKCC1 basal activity did not show gender differences in intact aortic rings, but in the presence of PE, bumetanide-sensitive 86Rb +/K + uptake increased more in male than female aortas (179 ± 8 in males vs 158 ± 5 nmol 86Rb +/K + min -1 (g aorta) -1 in females; P < 0.05). PE did not stimulate NKCC1 activity in denuded aorta from male rats. However, in female rats, PE increased NKCC1 activity similarly in both denuded (169 ± 11 nmol 86Rb +/K + min -1 (g aorta) -1) and intact aortas. Ovariectomy increased the bumetanide-sensitive 86Rb +/K + uptake increase elicited by PE (223 ± 17 nmol 86Rb +/K + min -1 (g aorta) -1) and hormone replacement with 17β-estradiol prevented this effect (159 ± 29 nmol 86Rb +/K + min -1 (g aorta) -1). Na +,K +-ATPase basal activity, measured as ouabain-sensitive 86Rb +/K + uptake, was similar in male and female rats, but the effect of PE was significantly less in intact male aortas (232 ± 16 in males vs 296 ± 25 nmol 86Rb +/K + min -1 (g aorta) -1 in females; P < 0.05). Our results suggest that PE induced activation of NKCC1 and Na +,K +-ATPase in the rat aorta in a gender-dependent way. © 2006 Nature Publishing Group. All rights reserved.

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Título según WOS: Na+-K+-2Cl(-) cotransporter is implicated in gender differences in the response of the rat aorta to phenylephrine
Título según SCOPUS: Na +-K +-2Cl - cotransporter is implicated in gender differences in the response of the rat aorta to phenylephrine
Título de la Revista: BRITISH JOURNAL OF PHARMACOLOGY
Volumen: 148
Número: 7
Editorial: WILEY-BLACKWELL
Fecha de publicación: 2006
Página de inicio: 964
Página final: 972
Idioma: English
URL: http://doi.wiley.com/10.1038/sj.bjp.0706818
DOI:

10.1038/sj.bjp.0706818

Notas: ISI, SCOPUS