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Hypertension
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Hypertension. 2001;38:592-596
doi: 10.1161/hy09t1.096248
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(Hypertension. 2001;38:592.)
© 2001 American Heart Association, Inc.


Cardiovascular Biology

Ca2+ Influx is Increased in 2-Kidney, 1-Clip Hypertensive Rat Aorta

Glaucia Elena Callera; Wamberto Antonio Varanda; Lusiane Maria Bendhack

Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences (G.E.C., L.M.B.), and Department of Physiology, Faculty of Medicine (W.A.V.), University of São Paulo, Ribeirão Preto, São Paulo.

Correspondence to Lusiane M. Bendhack, Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Av. do Café s/no., 14040-903 Ribeirão Preto, SP- Brazil. E-mail bendhack{at}usp.br

Abstract

Abstract— Arteries from hypertensive rats show a greater contraction in response to Ca2+ channel activator and an increased sensitivity to Ca2+ entry blockers compared with those of normotensive rats. These facts suggest an altered Ca2+ influx through membrane channels. In this study, this hypothesis was tested 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 membrane potential of smooth muscle cells is an important regulator of the conformational state of L-type Ca2+ 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 [pD2], 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; pD2, 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 Ca2+ concentration ([Ca2+]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 [Ca2+]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 Ca2+ influx through voltage-gated Ca2+ channels.


Key Words: hypertension, renal vascular • rats • blood vessels • calcium




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