Rho kinase inhibitors reduce voltage-dependent Ca~(2+) channel signaling in aortic and renal microvascular smooth muscle cells

摘要

Y-27632 (5 p,M) also significantly attenuated Bay K8644-induced vasoconstriction (P < 0.05). Changes in intracellular Ca~(2+) concentration ([Ca~(2+)]i) were estimated by fura-2 fluorescence during KCl-induced depolarization in cultured A7r5 cells and in freshly isolated preglomerular microvascular smooth muscle cells. Administration of 90 mM KC1 significantly increased fura-2 fluorescence in both cell types. KC1-mediated elevation of [Ca~(2+)]i in A7r5 cells was suppressed by 1-10 |xM Y-27632 (P < 0.05), but 10 |xM Y-27632 was required to suppress Ca~(2+) responses in preglomerular microvascular smooth muscle cells. RKI-1447, however, significantly attenuated KC1-medi-ated elevation of [Ca~(2+)]_i. Y-27632 markedly inhibited Bay K8644-induced elevation of [Ca~(2+)]_i in both cell types. The results of the present study indicate that the Rho kinase inhibitors Y-27632 and RKI-1447 can partially inhibit L-VDCC function and participate in L-VDCC signaling.