BMC Ear, Nose and Throat Disorders

Background: Vasospasm of the spiral modiolar artery (SMA) may cause ischemic stroke of the inner ear. Endothelin-1 (ET-1) induces a strong, long-lasting constriction of the SMA by increasing contractile apparatus Ca2+ sensitivity via Rho-kinase. We therefore tested several Rho-kinase inhibitors and a cell-permeable analogue of cAMP (dbcAMP) for their ability to reverse ET-1induced constriction and Ca2+-sensitization. Methods: The present study employed SMA isolated from gerbil temporal bones. Ca2+sensitivity was evaluated by correlating vascular diameter and smooth muscle cell [Ca]i, measured by fluo4-microfluorometry and videomicroscopy. Results: The Rho-kinase inhibitors Y-27632, fasudil, and hydroxy-fasudil reversed ET-1-induced vasoconstriction with an IC50 of 3, 15, and 111 μmol/L, respectively. DbcAMP stimulated a dosedependent vasodilation (Ec50 = 1 mmol/L) and a reduction of [Ca]i (EC50 = 0.3 μmol/L) of ET-1preconstricted vessels (1 nmol/L). Fasudil and dbcAMP both reversed the ET-1-induced increase in Ca2+ sensitivity. Conclusion: Rho-kinase inhibition and dbcAMP reversed ET-1-induced vasoconstriction and Ca2+-sensitization. Therefore, Rho-kinase inhibitors or cAMP modulators could possess promise as pharmacological tools for the treatment of ET-1-induced constriction, ischemic stroke and sudden hearing loss. Background The inner ear's blood supply depends solely on the spiral modiolar artery (SMA), a functional end artery. Vasospasm/constriction of the SMA can cause an ischemic stroke of the inner ear, leading to sudden sensorineural hearing loss (SSHL). Thus, investigating the mechanisms controlling the inner ear microcirculation is a prerequisite for the development of new strategies to treat SSHL. Capillary blood flow is primarily regulated by the resistance of precapillary arteries. The vascular resistance is a function of the contractile status of the vascular smooth muscle cells (VSMCs). Constriction of VSMCs results from Published: 29 November 2005 BMC Ear, Nose and Throat Disorders 2005, 5:10 doi:10.1186/1472-6815-5-10 Received: 16 June 2005 Accepted: 29 November 2005 This article is available from: http://www.biomedcentral.com/1472-6815/5/10 © 2005 Scherer et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.