Increased (Na+K+Cl) cotransport in rat arterial smooth muscle in deoxycorticosterone (DOCA)/salt-induced hypertension.
The inhibition by loop diuretics of K efflux (tracer (86)Rb) from the rat femoral arterial smooth muscle was measured in normotension and in DOCA-salt hypertension. The sensitivity sequence (bumetanide > piretanide > furosemide) was the characteristic pharmacological profile of (Na+K+Cl) cotransport. In hypertension, cotransport activity was 46% greater than in normotension and the sensitivity to loop diuretics was threefold less. Intracellular ¿K and the Na, K and Cl permeability ratios and electrogenic Na pump activity were assessed electrophysiologically in normotension and hypertension. ¿K(i) was lower in hypertension (173 mM) than normotension (198 mM) but the other parameters (P(Na/Cl) = 0.14, P(Cl)/P(K) = 0.19 and electrogenic pump = -8.3 mV in normotension) were not significantly different. Ionic permeabilities to Na, K and Cl were significantly lower in hypertension than normotension. Plasma ¿Na, but not ¿K, was higher in hypertension than normotension. The conclusion is that increased activation of (Na+K+Cl) cotransport in hypertension plays a major role in the elevation of ¿Cl(i) and depolarisation of the membrane potential in vascular smooth muscle in DOCA-salt hypertension. The role of (Na+K+Cl) cotransport in vascular smooth muscle in this model of hypertension is discussed in relation to ¿Cl(i), depolarisation of the membrane potential and contraction and in relation to cell growth.
Brown
R A
RA
Department of Mathematics, University of Dundee, UK.
Chipperfield
A R
AR
Davis
J P
JP
Harper
A A
AA
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D003900:Desoxycorticosterone; D004232:Diuretics / Q000494:pharmacology; D004912:Erythrocytes / Q000737:chemistry; D005665:Furosemide / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017136:Ion Transport; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010949:Plasma / Q000737:chemistry; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
D002712:Chlorides; D004232:Diuretics; D013449:Sulfonamides; D002034:Bumetanide; D003900:Desoxycorticosterone; D005665:Furosemide; D012964:Sodium; C015451:piretanide; D011188:Potassium