Ropivacaine attenuates pulmonary vasoconstriction induced by thromboxane A(2) analogue in the isolated perfused rat lung

Background and Objectives: Thromboxane A(2) (TXA(2)) activation is involved in several pathophysiological states in producing pulmonary hypertension. Local anesthetics (LA) inhibit signaling of TXA(2) receptors expressed in c ell models. Therefore, we hypothesized that LA may inhibit pulmonary vasoco nstriction induced by the TXA(2) analogue U 46619 in an isolated lung model . Methods: Isolated rat lungs were perfused with physiological saline solutio n and autologous blood with or without the LA lidocaine, bupivacaine, ropiv acaine, or the permanently charged lidocaine analogue QX 314 (all 1 mu g/mL ) as a pretreatment. Subsequently, pulmonary vasoconstriction was induced b y 3 concentrations of U 46619 (25, 50, and 100 ng/mL) and the change in pul monary artery pressure (P-a) was compared with each LA. In a second experim ent, P-a responses to angiotensin II (0.1 mu g), hypoxic pulmonary vasocons triction (HPV, 3% O-2 for 10 minutes),or phenylephrine (0.1 mu g) were asse ssed to determine the specificity of ropivacaine effects on TXA(2), recepto rs. Finally, reversibility of pulmonary vasoconstriction was determined by adding ropivacaine to the perfusate after pulmonary vasoconstriction was es tablished with U 46619. Results: Ropivacaine, but nut bupivacaine, lidocaine, or QX 314 significant ly attenuated pulmonary vasoconstriction induced by 50 ng/mL U 46619 (35.9% , P < .003) or 100 ng/mL U 46619 (45.2%, P < .001). This effect of ropivaca ine was likely to be specific for the thromboxane receptor because pulmonar y vasoconstriction induced by angiotensin II, HPV, or phenylephrine was not altered. Ropivacaine did not reverse vasoconstriction when it was administ ered after U 46619. Conclusions: Ropivacaine, but not lidocaine, bupivacaine, or QX 314 at 1 mu g/mL, attenuates U 46619-induced pulmonary vasoconstriction in an isolated perfused rat lung model. These results support evidence that the clinicall y used enantiomer S(-)-ropivacaine may inhibit TXA(2) signaling.