ROLE OF K-ATP CHANNELS ON MODULATING DIAPHRAGMATIC MICROVASCULAR FLOWDURING HEMORRHAGIC HYPOTENSION

The effects of glibenclamide (GLB), a specific blocker of ATP-sensitiv e potassium (K-ATP) channels, and tetraethylammonium (TEA) on modulati ng the regulation of diaphragmatic microcirculation were assessed in a nesthetized mechanically ventilated rats. With bicarbonate-buffered Ri nger solution continuously suffusing the left hemidiaphragm, microcirc ulatory blood flow was recorded by laser-Doppler flowmetry (Q over dot (LDF)) Hemorrhagic hypotension (HH) was induced via bleeding into a pr essure reservoir. Five sets of experiments were performed. In set 1 (n = 6), the vasodilator effect of diazoxide (3 x 10(-4) M) was abolishe d after a 30-min suffusion with GLB, whereas the vasodilator effect of sodium nitroprusside (3 x 10(-6) M) remained the same. In set 2 (vehi cle + HH; n = 23), a stepwise reduction in systemic arterial blood pre ssure (ABP) induced two distinct patterns of microvascular responses. Regulation of Q over dot(LDF) could be observed in pattern A animals i n a range of ABP from 113 to 52 mmHg, whereas Q over dot(LDF) in patte rn B animals rose progressively with declining ABP. In set 3 (GLB + HH ; n = 17), baseline values of Q over dot(LDF) were not significantly a ffected after a 30-min suffusion of GLB (10(-5) M). During HH, two mic rovascular patterns similar to those in set 2 were observed. GLB signi ficantly potentiated the reduction in Q over dot(LDF) in pattern A ani mals. In contrast, GLB had no effect on Q over dot(LDF) in pattern B a nimals. In set 4 (TEA f HH; n = 17), similar microvascular responses, compared with the vehicle group, were observed during HH after a 30-mi n suffusion of TEA (2 x 10(-3) M). In set 5 (n = 5), baseline values o f Q over dot(LDF) were not significantly altered during sham hypotensi on. We conclude that 1) K-ATP channels are functional but not active i n the resting diaphragmatic microcirculation and 2) K-ATP channels can modulate regulation of the microcirculation in the resting diaphragm during HH.