Vasoconstrictors and nitrovasodilators reciprocally regulate the Na+-K+-2Cl- cotransporter in rat aorta

Little is knownabout the function and regulation of theNa⁺-K⁺-2Clcotransporter NKCC1 in vascular smooth muscle. Theactivity of NKCC1 was measured as the bumetanide-sensitive efflux of⁸⁶Rb⁺from intact smooth muscle of the rat aorta. Hypertonic shrinkage (440 mosmol/kgH₂O) rapidlydoubled cotransporter activity, consistent with its volume-regulatoryfunction. NKCC1 was also acutely activated by the vasoconstrictors ANGII (52%), phenylephrine (50%), endothelin (53%), and 30 mM KCl(54%). Both nitric oxide and nitroprusside inhibited basal NKCC1activity (39 and 34%, respectively), and nitroprussidecompletely reversed the stimulation by phenylephrine. Thephosphorylation of NKCC1 was increased by hypertonic shrinkage, phenylephrine, and KCl and was reduced by nitroprusside. The inhibition of NKCC1 significantly reduced the contraction of rat aorta induced byphenylephrine (63% at 10 nM, 26% at 30 nM) but not by KCl. Weconclude that theNa⁺-K⁺-2Clcotransporter in vascular smooth muscle is reciprocally regulated byvasoconstrictors and nitrovasodilators and contributes to smooth musclecontraction, indicating that alterations in NKCC1 could influencevascular smooth muscle tone in vivo.