Potentiation of stretch-induced tone in the rabbit facial vein by an isoquinoline derivative, LOE 908

Abstract

The rabbit facial vein exhibits extracellular Ca2+- and temperature-dependent spontaneous myogenic tone in response to stretch. The present study aimed to elucidate pharmacological characteristics of Ca2+ entry mechanisms responsible for the stretch-induced tension development of the rabbit facial vein. Ca2+- and temperature-sensitive vascular tone in response to stretch was refractory to L-type Ca2+ channel blockers such as nifedipine and diltiazem but was abolished by papaverine or SK&F 96365 which blocks both receptor- and store-operated Ca2+ channels. Interestingly, LOE 908, another type of voltage-independent Ca2+-permeable channel blocker, showed augmentation of the stretch-induced vascular tone instead of inhibition. Potentiation by LOE 908 of stretch-induced vascular tone was also extracellular Ca2+-dependent and counteracted by SK&F 96365. Membrane stretch-activated Ca2+ channels in the rabbit facial vein smooth muscle cells may have a unique characteristic that their opening is stimulated by LOE 908 and thus is distinguishable from other voltage-independent Ca2+-permeable channels.