title: Na(+)-K+ pump and Na(+)-K+ co-transport in cultured vascular smooth muscle cells from spontaneously hypertensive and normotensive rats: baseline activity and regulation.
abstract: OBJECTIVE
  This paper examines the hypothesis that aberrations in vascular smooth muscle univalent ion transport systems play an important role in the pathogenesis of hypertension.
  
  
  METHODS
  Baseline Na(+)-K+ pump and Na(+)-K(+)-2Cl- co-transport activities and the regulation of these ion transport systems by angiotensin II and second messenger molecules have been studied in cultured aortic smooth muscle cells (VSMC) from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).
  
  
  METHODS
  Ion transport was studied using isotopic univalent cations (86Rb and 22Na).
  
  
  RESULTS
  Baseline Na(+)-K+ pump activity was comparable between SHR- and WKY-derived VSMC. Baseline Na(+)-K(+)-2Cl- and K(+)-Cl- co-transport activity as well as K+ leakage were significantly greater in SHR VSMC. Baseline Na(+)-K(+)-2Cl- co-transport was sensitive to inhibition by forskolin and ethyleneglycol-bis-(beta-amino ethylester)-N,N,N',N'-tetraacetic acid, whereas cyclic guanosine monophosphate and phorbol 12-myristate, 13-acetate had no effect. Angiotensin II-stimulated Na(+)-K(+)-2Cl- co-transport activity did not differ between WKY and SHR VSMC. Angiotensin II increased Na(+)-K(+)-pump activity to a significantly greater extent in SHR VSMC. The stimulatory effect of angiotensin II upon Na(+)-K+ pump activity was reduced under Na(+)-free buffer conditions and in the presence of the Na(+)-H+ exchange inhibitor, ethylisopropyl amiloride. Na(+)-K+ pump activity was also stimulated by the protein kinase C activator, phorbol 12-myristate, 13-acetate, and this was completely inhibited under Na(+)-free buffer conditions.
  
  
  CONCLUSIONS
  SHR VSMC exhibit anomalous Na(+)-K(+)-pump and Na(+)-K(+)-2Cl- co-transport activities. The influence of these univalent ion transport systems upon cellular Na+ and Ca2+ homeostasis invoke their participation in the pathogenesis of hypertension.
authors.affiliation: Department of Research, Basel University Hospital, Switzerland.
authors.forename: S N
authors.initials: SN
authors.lastname: Orlov
authors.forename: T J
authors.initials: TJ
authors.lastname: Resink
authors.forename: J
authors.initials: J
authors.lastname: Bernhardt
authors.forename: F R
authors.initials: FR
authors.lastname: Bühler
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012414:Rubidium Radioisotopes; D015290:Second Messenger Systems / Q000502:physiology; D012979:Sodium Radioisotopes; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D012414:Rubidium Radioisotopes; D012979:Sodium Radioisotopes; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D000804:Angiotensin II; D000254:Sodium-Potassium-Exchanging ATPase