EFFECT OF DESFLURANE AND HALOTHANE ON PHENYLEPHRINE-INDUCED CONTRACTION IN ISOLATED RAT AORTIC SMOOTH MUSCLE

Abstract

Introduction. The local interaction between desflurane and sympathetic agonists remains unclear. An increase in desflurane concentration results in sympathetic activation which is not fully inhibited by blockade of airway irritation [1]. In vivo studies on chronically instrumented animals demonstrate a reduced systemic vascular resistance. Therefore, we compared the direct interaction of desflurane and halothane with phenylephrine (PE) in an isolated vascular smooth muscle preparation. A second series of experiments investigated the influence of nitric oxide (NO) inhibition on the effect of desflurane on a similar preparation. Methods. 36 300-400 gram male Wistar rats were studied. Endothelial-free 3 mm thoracic aortic rings were suspended from a force transducer in oxygenated modified Krebs-Ringer bicarbonate solution at 37[degree sign]C. A dose-response curve was constructed for each preparation using 10-7 M, 10-6 M and 10-5 M PE and repeated in the presence of both 2 MAC desflurane and halothane (n=16). A second series of experiments examined the effect of 1, 2 and 3 MAC desflurane and halothane on 10-6 M PE contractions (n=12). Finally, we examined the effect of a NO antagonist, NG-nitro-L-arginine (L-NNA) on contractions of an endothelial-intact preparation in the presence of desflurane (n=8). Statistical analysis was with the paired two-tailed student's t-test and repeated measures ANOVA. Results. Contractions were significantly greater at 10-6 and 10 (-5) M PE in the presence of 2 MAC desflurane (p<0.05) (Figure 1). ANOVA demonstrated a significant difference between the desflurane and halothane data (p=0.03). 1 and 2 MAC desflurane significantly increased contraction amplitude in response to 10 (-6) M PE (p<0.05). Halothane significantly reduced contraction amplitude at 3 MAC (p<0.05). ANOVA revealed a significant difference between the two curves (p=0.02). In the presence of L-NNA, desflurane had a greater effect (Figure 2).Figure 1Figure 2Discussion. Desflurane may cause local catecholamine release from nerve endings which may explain the interaction with phenylephrine. NO inhibition appears to increase the effect. This study may have implications for anaesthetic management of vasopressor-dependent or septic patients.