Effect of tetrodotoxin on membrane potentials and active tone in vascular smooth muscle

The suitability of tetrodotoxin (TTX) for studies of the neural control of vascular smooth muscle (VSM) tone in the microcirculation was evaluated by determining 1) whether TTX blockade of neural input to adrenergically innervated VSM is reversible and 2) whether TTX depresses active VSM tone directly. Diameters of rat mesenteric veins and third- and fourth-order arterioles of the hamster cheek pouch were measured by image splitting. VSM transmembrane potentials (Em) were measured with microelectrodes in rat mesenteric veins. In the veins TTX suffusion (10(-6) g/ml) resulted in dilation and reversible Em hyperpolarization. TTX also reversibly blocked the venoconstrictor response to perivascular nerve stimulation. TTX had no effect on the resting tone of hamster arterioles or on arteriolar constriction in response to increased oxygen availability. TTX did not affect the response to norepinephrine in either preparation. This study indicates that TTX specifically and reversibly blocks VSM responses to neural activation but that it has no direct depressant effect on resting VSM tone or active constriction in response to nonneural activation.