Na(+)-K+ pump and Na(+)-K+ co-transport in cultured vascular smooth muscle cells from spontaneously hypertensive and normotensive rats: baseline activity and regulation.
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.
Orlov
S N
SN
Department of Research, Basel University Hospital, Switzerland.
Resink
T J
TJ
Bernhardt
J
J
Bühler
F R
FR
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*
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