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.