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

Javier Palacios, Francisco Espinoza, Carolina Munita, Fredi Cifuentes, Luis Michea

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)964-972
Number of pages9
JournalBritish Journal of Pharmacology
Volume148
Issue number7
DOIs
StatePublished - 12 Aug 2006

Keywords

  • Bumetanide
  • Ouabain
  • Phenylephrine
  • Rat aorta
  • Vascular contraction

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