Ca2+ influx is increased in 2-kidney, 1-clip hypertensive rat aorta

Arteries from hypertensive rats show a greater contraction in response to C a2+ channel activator and an increased sensitivity to Ca2+ entry blockers c ompared with those of normotensive rats. These facts suggest an altered Ca2 + influx through membrane channels. In this study, this hypothesis was test ed by direct activation of voltage-gated Ca2+ channels using Bay K 8644, a dihydropyridine sensitive large conductance (L-type) Ca2+ channel opener in aortas from 2-kidney, 1-clip (2K1C) hypertensive rats. Because the membran e potential or smooth muscle cells is an important regulator of the conform ational state of L-type Ca2+ channels and, consequently, dihydropyridine af finity, the effect of 10 mmol/L KC1 on the responses to Bay K 8644 was also studied. Maximal contraction (ME) and sensitivity to Bay K 8644 were great er 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 KC1 concentration was increased from 4.7 to 10 mmol/L in the bathing medium, no differences were observed in the contractile effect of B ay 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 o f 2K1C aorta vascular smooth muscle cells were less negative than in 2K (-3 5.19 +/-4.91 versus -48.32 +/-1.88 mV). Basal intracellular Ca2+ concentrat ion ([Ca2+](i)) Was greater in cultured vascular smooth muscle cells from 2 K1C than from 2K (293.4 +/- 25.83 versus 205.40 +/- 12.83 nmol/L). In 2K1C, Bay K 8644 induced a larger increase in [Ca2+](1), than in 2K (190.60 +/- 45.65 versus 92.57 +/- 14.67 nmol/L), and in 10 mmol/L KC1, 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 t o Bay K 8644 in 2K1C aortas is due to an increased Ca2+ influx through volt age-gated Ca2+ channels.