K-Cl cotransport in vascular smooth muscle and erythrocytes: possible implication in vasodilation.
K-Cl cotransport, the electroneutral-coupled movement of K and Cl ions, plays an important role in regulatory volume decrease. We recently reported that nitrite, a nitric oxide derivative possessing potent vasodilation properties, stimulates K-Cl cotransport in low-K sheep red blood cells (LK SRBCs). We hypothesized that activation of vascular smooth muscle (VSM) K-Cl cotransport by vasodilators decreases VSM tension. Here we tested this hypothesis by comparing the effects of commonly used vasodilators, hydralazine (HYZ), sodium nitroprusside, isosorbide mononitrate, and pentaerythritol, on K-Cl cotransport in LK SRBCs and in primary cultures of rat VSM cells (VSMCs) and of HYZ-induced K-Cl cotransport activation on relaxation of isolated porcine coronary rings. K-Cl cotransport was measured as the Cl-dependent K efflux or Rb influx in the presence and absence of inhibitors for other K/Rb transport pathways. All vasodilators activated K-Cl cotransport in LK SRBCs and HYZ in VSMCs, and this activation was inhibited by calyculin and genistein, two inhibitors of K-Cl cotransport. KT-5823, a specific inhibitor of protein kinase G, abolished the sodium nitroprusside-stimulated K-Cl cotransport in LK SRBCs, suggesting involvement of the cGMP pathway in K-Cl cotransport activation. Hydralazine, in a dose-dependent manner, and sodium nitroprusside relaxed (independently of the endothelium) precontracted arteries when only K-Cl cotransport was operating and other pathways for K/Rb transport, including the Ca-activated K channel, were inhibited. Our findings suggest that K-Cl cotransport may be involved in vasodilation.
Adragna
N C
NC
Departments of Pharmacology and Toxicology, Wright State University, School of Medicine, Dayton, Ohio 45435, USA. norma.adragna@wright.edu
White
R E
RE
Orlov
S N
SN
Lauf
P K
PK
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002227:Carbazoles; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000493:pharmacokinetics*; D003331:Coronary Vessels / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D005033:Ethylmaleimide / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D007211:Indoles; D007537:Isometric Contraction / Q000502:physiology; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000494:pharmacology; D008387:Marine Toxins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D011188:Potassium / Q000493:pharmacokinetics*; D011409:Propylene Glycols / Q000494:pharmacology; D051381:Rats; D012413:Rubidium / Q000493:pharmacokinetics; D012756:Sheep; D013552:Swine; D027981:Symporters; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D000096922:K Cl- Cotransporters
D000470:Alkaloids; D002227:Carbazoles; D002352:Carrier Proteins; D002712:Chlorides; D004791:Enzyme Inhibitors; D005033:Ethylmaleimide; D019833:Genistein; D006830:Hydralazine; D007211:Indoles; D007548:Isosorbide Dinitrate; D008387:Marine Toxins; D009569:Nitric Oxide; D009599:Nitroprusside; D010080:Oxazoles; D011188:Potassium; D011409:Propylene Glycols; D012413:Rubidium; D027981:Symporters; D014665:Vasodilator Agents; D000096922:K Cl- Cotransporters; C073601:KT 5823; C059041:calyculin A; C030397:isosorbide-5-mononitrate; C008783:pentaerythritol