Jm. Simard et al., INCREASE IN FUNCTIONAL CA2-MUSCLE WITH RENAL-HYPERTENSION( CHANNELS IN CEREBRAL SMOOTH), Circulation research, 82(12), 1998, pp. 1330-1337
Citations number
43
Categorie Soggetti
Hematology,"Peripheal Vascular Diseas","Cardiac & Cardiovascular System
The hypothesis that availability of functional Ca2+ channels in vascul
ar smooth muscle is augmented in hypertension was tested in basilar ar
tery cells from Wistar rats exhibiting stable systolic blood pressure
(BPsys) for 2 to 11 weeks after partial renal artery ligation (Goldbla
tt 2-kidney 1-clip [2K1C] model). Cells were freshly isolated and patc
h-clamped using a nystatin-perforated patch method. BPsys ranged from
110 to 280 mm Hg and correlated with normalized kidney mass. Macroscop
ic current-voltage curves were fit to a Boltzmann function to obtain m
aximum conductance (g(max)), steepness and midpoint potential for the
voltage dependence of activation (k and E-1/2, respectively), and extr
apolated reversal potential for the chord conductance (E-rev). Linear
regression of normalized conductance (ng(max)=g(max)/cell capacitance)
versus BPsys for 103 cells indicated a strong relationship, with a sl
ope of 0.0019 nS.pF(-1).mm Hg-1 (P<0,0001). Similar analysis of data f
rom 35 other cells exposed to 500 nmol/L Bay K 8644 gave a slope of 0.
0041 nS.pF(-l) .mm Hg-1 (P=0.001). Voltage-dependent parameters, k, E-
1/2, and E-rev, were not significantly related to BPsys. Single-channe
l measurements in cell-attached patches revealed chat the number of ch
annels in 32 patches was significantly related to BPsys (P=0.0024) but
that slope conductance, open dwell times at 0 mV, and distribution be
tween 2 open states were not. Finally, in a subgroup of 61 cells from
animals made hypertensive (180 mm HE<BPsys<200 mmHg) for approximate t
o 1/2 to 6 weeks, we found that elevation of ng(max) depended on durat
ion of hypertension (P=0,003), with no elevation at approximate to 1/2
week. We conclude that in the 2K1C model, availability of functional
Ca2+ channels increases with BPsys with no change in channel propertie
s and that measurable BPsys elevation occurs before the increase in fu
nctional channels.