Increase in Functional Ca Channels in Cerebral Smooth Muscle With Renal Hypertension

The hypothesis that availability of functional Ca channels in vascular smooth muscle is augmented in hypertension was tested in basilar artery cells from Wistar rats exhibiting stable systolic blood pressure (BPsys) for 2 to 11 weeks after partial renal artery ligation (Goldblatt 2-kidney 1-clip [2K1C] model). Cells were freshly isolated and patch-clamped using a nystatin–perforated patch method. BPsys ranged from 110 to 280 mm Hg and correlated with normalized kidney mass. Macroscopic current-voltage curves were fit to a Boltzmann function to obtain maximum conductance (gmax), steepness and midpoint potential for the voltage dependence of activation (k and E1/2, respectively), and extrapolated reversal potential for the chord conductance (Erev). Linear regression of normalized conductance (ngmax5gmax/cell capacitance) versus BPsys for 103 cells indicated a strong relationship, with a slope of 0.0019 nS z pF z mm Hg (P,0.0001). Similar analysis of data from 35 other cells exposed to 500 nmol/L Bay K 8644 gave a slope of 0.0041 nS z pF z mm Hg (P50.001). Voltage-dependent parameters, k, E1/2, and Erev, were not significantly related to BPsys. Single-channel measurements in cell-attached patches revealed that the number of channels in 32 patches was significantly related to BPsys (P50.0024) but that slope conductance, open dwell times at 0 mV, and distribution between 2 open states were not. Finally, in a subgroup of 61 cells from animals made hypertensive (180 mm Hg,BPsys,200 mm Hg) for '1/2 to 6 weeks, we found that elevation of ngmax depended on duration of hypertension (P50.003), with no elevation at '1/2 week. We conclude that in the 2K1C model, availability of functional Ca channels increases with BPsys with no change in channel properties and that measurable BPsys elevation occurs before the increase in functional channels. (Circ Res. 1998;82:1330-1337.)