Ca(2+) influx is increased in 2-kidney, 1-clip hypertensive rat aorta.

Abstract

Arteries from hypertensive rats show a greater contraction in response to Ca(2+) channel activator and an increased sensitivity to Ca(2+) entry blockers compared with those of normotensive rats. These facts suggest an altered Ca(2+) influx through membrane channels. In this study, this hypothesis was tested by direct activation of voltage-gated Ca(2+) channels using Bay K 8644, a dihydropyridine sensitive large conductance (L-type) Ca(2+) channel opener in aortas from 2-kidney, 1-clip (2K1C) hypertensive rats. Because the membrane potential of smooth muscle cells is an important regulator of the conformational state of L-type Ca(2+) channels and, consequently, dihydropyridine affinity, the effect of 10 mmol/L KCl on the responses to Bay K 8644 was also studied. Maximal contraction (ME) and sensitivity to Bay K 8644 were greater in 2K1C rats than in 2K normotensive rats (ME, 1.77+/-0.15 versus 1.25+/-0.19 g; negative log molar value [pD(2)], 8.27+/-0.07 versus 7.92+/-0.08). When the KCl concentration was increased from 4.7 to 10 mmol/L in the bathing medium, no differences were observed in the contractile effect of Bay K 8644 between 2K1C and 2K (ME, 1.28+/-0.13 versus 1.14+/-0.21 g; pD(2), 8.56+/-0.08 versus 8.38+/-0.07). The cell resting membrane potential of 2K1C aorta vascular smooth muscle cells were less negative than in 2K (-35.19+/-4.91 versus -48.32+/-1.88 mV). Basal intracellular Ca(2+) concentration ([Ca(2+)](i)) was greater in cultured vascular smooth muscle cells from 2K1C than from 2K (293.4+/-25.83 versus 205.40+/-12.83 nmol/L). In 2K1C, Bay K 8644 induced a larger increase in [Ca(2+)](i) than in 2K (190.60+/-45.65 versus 92.57+/-14.67 nmol/L), and in 10 mmol/L KCl, this difference was abolished (134.90+/-45.12 versus 125.20+/-32.17 nmol/L). The main conclusion of the present work is that the increased contractile response to Bay K 8644 in 2K1C aortas is due to an increased Ca(2+) influx through voltage-gated Ca(2+) channels.