Role of KATP channels on modulating diaphragmatic microvascular flow during hemorrhagic hypotension.
The effects of glibenclamide (GLB), a specific blocker of ATP-sensitive potassium (KATP) channels, and tetraethylammonium (TEA) on modulating the regulation of diaphragmatic microcirculation were assessed in anesthetized mechanically ventilated rats. With bicarbonate-buffered Ringer solution continuously suffusing the left hemidiaphragm, microcirculatory blood flow was recorded by laser-Doppler flowmetry (QLDF). Hemorrhagic hypotension (HH) was induced via bleeding into a pressure reservoir. Five sets of experiments were performed. In set 1 (n = 6), the vasodilator effect of diazoxide (3 x 10(-4) M) was abolished 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 (vehicle + HH; n = 23), a stepwise reduction in systemic arterial blood pressure (ABP) induced two distinct patterns of microvascular responses. Regulation of QLDF could be observed in pattern A animals in a range of ABP from 113 to 52 mmHg, whereas QLDF in pattern B animals rose progressively with declining ABP. In set 3 (GLB + HH; n = 17), baseline values of QLDF were not significantly affected after a 30-min suffusion of GLB (10(-5) M). During HH, two microvascular patterns similar to those in set 2 were observed. GLB significantly potentiated the reduction in QLDF in pattern A animals. In contrast, GLB had no effect on QLDF in pattern B animals. In set 4 (TEA + HH; n = 17), similar microvascular responses, compared with the vehicle group, were observed during HH after a 30-min suffusion of TEA (2 x 10(-3) M). In set 5 (n = 5), baseline values of QLDF were not significantly altered during sham hypotension. We conclude that 1) KATP channels are functional but not active in the resting diaphragmatic microcirculation and 2) KATP channels can modulate regulation of the microcirculation in the resting diaphragm during HH.
Chang
H Y
HY
Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Chen
C W
CW
Hsiue
T R
TR
Chen
C R
CR
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003964:Diaphragm / Q000098:blood supply*; D003981:Diazoxide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006470:Hemorrhage / Q000503:physiopathology*; D007022:Hypotension / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D009599:Nitroprusside; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide