Mechanisms of U46619- and 5-HT-induced contraction of bovine pulmonary arteries: role of chloride ions

Thromboxane A2 and 5-hydroxytryptamine (5-HT) are implicated in pulmonary hypertension. The involvement of chloride, voltage-operated calcium channels (VOCCs), store-operated calcium channels (SOCCs) and the Rho kinase in the contractile response of bovine pulmonary arteries (BPA) to the thromboxane A2 mimetic U46619 and 5-HT was investigated. This study suggests that the contractile response of BPA to U46619 involves Rho kinase together with a chloride-sensitive mechanism, which does not involve VOCC but may have a role in calcium release and calcium entry via SOCC. In contrast contraction of the BPA by 5-HT appears to involve verapamil- and mibefradil-sensitive VOCC. This study may indicate that the use of calcium channel blockers in the management of pulmonary hypertension may not always be effective and that Rho kinase and chloride channels may be targets for the development of new therapies.