Endothelium-dependent pulmonary vasodilation is selectively attenuated during isoflurane anesthesia

We have recently reported that halothane (Hal) anesthesia attenuates the pulmonary vasodilator responses to both bradykinin (BK) and sodium nitroprusside (SNP) compared with responses measured in the conscious state. These agonists have been classically used to activate endothelium-dependent and -independent vasodilator pathways, respectively. Our present goal was to assess the effect of isoflurane (Iso) anesthesia on pulmonary vasodilation activated via these pathways. Left pulmonary vascular pressure-flow (P-Q) plots were used to measure the pulmonary vascular responses to cumulative intravenous doses of BK, SNP, and 3-morpholinosydonimine-N-ethylcarbamide (SIN-1), a nitric oxide donor, in chronically instrumented dogs in the conscious state and during Iso anesthesia after matched preconstriction with the thromboxane analogue U-46619. Iso attenuated the vasodilator response to BK (P < 0.05). However, Iso had a differential effect on the responses to SIN-1 and SNP. Iso potentiated the vasodilator response to SIN-1 (P < 0.05), whereas Iso attenuated the response to SNP (P < 0.05). The vasodilator response to SIN-1 was unchanged during Hal anesthesia. The ATP-sensitive potassium (KATP)-channel inhibitor glibenclamide attenuated the vasodilator response to SNP (P < 0.05) but not to SIN-1. Thus Iso and Hal selectively attenuate the endothelium-dependent pulmonary vasodilator response to BK. Both anesthetics attenuate vasodilation induced by SNP but not by SIN-1. Moreover, a component of SNP-induced vasodilation involves KATP-channel activation.