Activation of Two Inward Chloride Transport Systems in Rat Femoral Arterial Smooth Muscle in Deoxycorticosterone Acetate/Salt Hypertension

1. Intracellular [Cl−] ([Cl−]i) was measured with ion-selective microelectrodes in rat femoral arterial smooth muscle in normotensive controls and after the induction of deoxycorticosterone acetate/salt hypertension. 2. Linear regression of [Cl−]i and time after the induction of hypertension showed good correlation (r = 0.96) for 5–6 weeks, as [Cl−]i increased from 30 ± 1 mmol/l (mean ± SD, n = 16), to 49 ± 2 mmol/l (n = 9, P < 0.0001). 3. Arterial systolic blood pressure also increased linearly (r = 0.97) for 5–6 weeks as hypertension developed from 122 ± 1 mmHg (n = 20) to 187 ± 7 mmHg (n = 14): there was consequently a linear relationship between [Cl−]i and arterial systolic blood pressure (r = 0.96). 4. The increase in [Cl−]i was partly because Na+−K+−Cl− co-transport activity, estimated from the fall in [Cl−]i caused by bumetanide, was greater in hypertension (18 mmol/l) than in normotension (10 mmol/l). This finding, and the depolarization of the membrane potential in hypertension (−56 ± 3 mV compared with −64 ± 4 mV in normotension; P < 0.0001), confirms previous studies. 5. The increase in [Cl−]i was also partly due to greater activity of an Na+- and HCO3−-independent, acetazolamide-sensitive inward Cl− transport system; thus acetazolamide reduced [Cl−]i by 7 mmol/l in normotension and by 16 mmol/l in hypertension. 6. In Cl−-free media, the membrane potential in normotension (−59 ± 5 mV) was not significantly different from that in hypertension (−60 ± 4 mV). 7. The role of [Cl−]i in the depolarization of the membrane potential in hypertension is discussed.