Endothelin-1–Induced Vasospasms of Spiral Modiolar Artery Are Mediated by Rho-Kinase–Induced Ca ²⁺ Sensitization of Contractile Apparatus and Reversed by Calcitonin Gene–Related Peptide

Abstract

ET-1 induces vasospasms of the spiral modiolar artery via ET(A) receptor-mediated activation of Rho-kinase, inhibition of myosin light chain phosphatase, and an increase in Ca(2+) sensitivity, which is reversed by CGRP. The observation that vasospasms were reversed by Y-27632 but not by BQ-123 or BMS-182874 suggests that Rho-kinase, rather than the ET(A) receptor, is the most promising pharmacological target for the treatment of ET-1-induced vasospasms, ischemic strokes, and sudden hearing loss.