Rho-Kinase Inhibitors Reduce Voltage-dependent Calcium Channel Signaling in Aortic and Renal Microvascular Smooth Muscle Cells.

Rho-Kinase Inhibitors Reduce Voltage-dependent Calcium Channel Signaling in Aortic and Renal Microvascular Smooth Muscle Cells.
Am J Physiol Renal Physiol. 2019 Aug 21;:
Authors: Guan Z, Baty JJ, Zhang S, Remedies CE, Inscho EW
Abstract
Voltage-dependent L-type calcium channels (L-VDCCs) and the rhoA/rho-kinase pathway are two predominant intracellular signaling pathways that regulate renal microvascular reactivity. Traditionally, these two pathways have been thought to act independently; however, recent evidence suggests these pathways could be convergent. We hypothesized that rho-kinase inhibitors can influence L-VDCC signaling. The effects of rho-kinase inhibitors Y-27632 or RKI-1447 on KCl-depolarization or the L-VDCC agonist, Bay K8644 were assessed in afferent arterioles using the in vitro blood-perfused rat juxtamedullary nephron preparation. Superfusion of KCl (30-90 mM) led to concentration-dependent vasoconstriction of afferent arterioles. Administration of Y-27632 (1, 5 and 10 µM) or RKI-1447 (0.1, 1 and 10 µM) significantly increased starting diameter by 16% to 65%. The KCl-induced vasoconstriction was markedly attenuated with 5 and 10 µM Y-27632, and 10 µM RKI-1447 (P<0.05 vs KCl alone). Y-27632 (5 µM) also significantly attenuated Bay K8644-induced vasoconstriction (P<0.05). Changes in intracellular calcium concentration ([Ca2+]i) were estimated by fura-2 fluorescence during KCl-depolarization in cultured A7r...

Source: American Journal of Physiology. Renal Physiology - August 20, 2019 Category: Physiology Authors: Guan Z, Baty JJ, Zhang S, Remedies CE, Inscho EW Tags: Am J Physiol Renal Physiol Source Type: research