Na+ -k+ -2cl- Cotransporter is Implicated in Gender Differences in the Response of the Rat Aorta to Phenylephrine.
From: Facultad de Ciencias, Dpto. de Ciencias Químicas y Farmacéuticas, Universidad Católica del Norte, Angamos 0610, Antofagasta, Casilla 1280 Chile. jpalacios@ucn.cl
British journal of pharmacology
- Publish Date: Aug 2006
- ISSN: 0007-1188
- Volume: 148
- Issue: 7
- Pages: 964-72
- Medium: Print
- Language: English
- Citation (JAMA): Palacios Javier, Espinoza Francisco, Munita Carolina, et al. Na+ -k+ -2cl- Cotransporter is Implicated in Gender Differences in the Response of the Rat Aorta to Phenylephrine.. Br. J. Pharmacol. Aug 2006;148:964-72
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 (86)Rb(+)/K(+) uptake increased more in male than female aortas (179+/-8 in males vs 158+/-5 nmol (86)Rb(+)/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 (86)Rb(+)/K(+) min(-1) (g aorta)(-1)) and intact aortas. Ovariectomy increased the bumetanide-sensitive (86)Rb(+)/K(+) uptake increase elicited by PE (223+/-17 nmol (86)Rb(+)/K(+) min(-1) (g aorta)(-1)) and hormone replacement with 17beta-estradiol prevented this effect (159+/-29 nmol (86)Rb(+)/K(+) min(-1) (g aorta)(-1)). Na(+),K(+)-ATPase basal activity, measured as ouabain-sensitive (86)Rb(+)/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 (86)Rb(+)/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.
Mesh Headings (Keywords): Acetylcholine, Animals, Aorta, Thoracic, Bumetanide, Cyclooxygenase Inhibitors, Diuretics, Endothelium, Vascular, Enzyme Inhibitors, Estradiol, Female, Indomethacin, Male, Muscle, Smooth, Vascular, Nitric Oxide Synthase Type III, Nitroarginine, Ovariectomy, Phenylephrine, Potassium, Rats, Rats, Sprague-Dawley, Rubidium Radioisotopes, Sex Characteristics, Sodium-Potassium-Chloride Symporters, Sodium-Potassium-Exchanging ATPase, Vasoconstrictor Agents, Vasodilator Agents
Check for Full Text / PubMed Unique Identifier (PMID): 16799647
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