The inhibition by loop diuretics of K efflux (tracer Rb-86) 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 CI 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 Ma, K and CI 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, Copyright(C) 1999 S. Karger AG, Basel.