Na+ -K+ -2Cl- cotransporter is implicated in gender differences in the response of the rat aorta to phenylephrine.
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.
Palacios
Javier
J
Facultad de Ciencias, Dpto. de Ciencias Químicas y Farmacéuticas, Universidad Católica del Norte, Angamos 0610, Antofagasta, Casilla 1280 Chile. jpalacios@ucn.cl
Espinoza
Francisco
F
Munita
Carolina
C
Cifuentes
Fredi
F
Michea
Luis
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010052:Ovariectomy; D010656:Phenylephrine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes; D012727:Sex Characteristics; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004232:Diuretics; D004791:Enzyme Inhibitors; D012414:Rubidium Radioisotopes; C578879:Slc12a2 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D002034:Bumetanide; D010656:Phenylephrine; D019335:Nitroarginine; D004958:Estradiol; D052250:Nitric Oxide Synthase Type III; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D011188:Potassium; D007213:Indomethacin