title: Blood pressure regulates the activity and function of the Na-K-2Cl cotransporter in vascular smooth muscle.
abstract: The Na-K-2Cl cotransporter (NKCC1) is one of several transporters that have been linked to hypertension, and its inhibition reduces vascular smooth muscle tone and blood pressure. NKCC1 in the rat aorta is stimulated by vasoconstrictors and inhibited by nitrovasodilators, and this is linked to the contractile state of the smooth muscle. To determine whether blood pressure also regulates NKCC1, we examined the acute effect of hypertension on NKCC1 in rats after aortic coarctation. In the hypertensive aorta (28-mmHg rise in mean blood pressure), an increase in NKCC1 activity (measured as bumetanide-sensitive (86)Rb efflux) was apparent by 16 h and reached a plateau of 62% greater than control at 48 h. In contrast, there was a slight decrease in NKCC1 activity in the hypotensive aorta (21% decrease in mean blood pressure). Measurement of NKCC1 mRNA by real-time PCR revealed a fivefold increase in the hypertensive aorta compared with the hypotensive aorta or sham aorta. The inhibition by bumetanide of isometric force response to phenylephrine was significantly greater in the hypertensive aorta than in the control aorta or hypotensive aorta. We conclude that NKCC1 in rat aortic smooth muscle is regulated by blood pressure, most likely through changes in transporter abundance. This upregulation of NKCC1 is associated with a greater contribution to force generation in the hypertensive aorta. This is the first demonstration that NKCC1 in vascular smooth muscle is regulated by blood pressure and indicates that this transporter is important in the acute response of vascular smooth muscle to hypertension.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Gengru
authors.initials: G
authors.lastname: Jiang
authors.forename: Fatma
authors.initials: F
authors.lastname: Akar
authors.forename: Scott L
authors.initials: SL
authors.lastname: Cobbs
authors.forename: Koba
authors.initials: K
authors.lastname: Lomashvilli
authors.forename: Randala
authors.initials: R
authors.lastname: Lakkis
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gordon
authors.forename: Roy L
authors.initials: RL
authors.lastname: Sutliff
authors.forename: W Charles
authors.initials: WC
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D001017:Aortic Coarctation / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D002034:Bumetanide / Q000494:pharmacology; D006332:Cardiomegaly / Q000503:physiopathology; D004232:Diuretics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D064506:Solute Carrier Family 12, Member 2
chemical_list: D004232:Diuretics; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C578879:Slc12a2 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide