Possible involvement of neuronal nitric oxide synthase enzyme in early-phase isoflurane-induced hypotension in rats.

This study was conducted to demonstrate the involvement of nitric oxide synthase (NOS) in the early-phase isoflurane-induced hypotension and to ascertain whether this NOS is neuronal NOS (nNOS) or endothelial NOS (eNOS). Mean arterial pressures (MAPs) were directly measured from the femoral arteries of urethane-anesthetized rats. Isoflurane-induced changes in MAP were monitored in rats following pretreatment with vehicle or one of the following NOS inhibitors: L-NG)monomethyl-L-arginine (L-NMMA), which is non-selective; L-NG)nitro arginine (L-NOARG), which is more selective for nNOS and eNOS; and 7-nitroindazole (7-NI), which is selective for nNOS. Exposure to 2% isoflurane in oxygen produced a triphasic reduction in MAP, including an early phase in which mean arterial pressure (MAP) fell by 25-30% during the initial 2(1/2) min. This early hypotensive response, but not subsequent phases, was abolished by i.v. pretreatment with either L-NMMA or L-NOARG. The early-phase hypotension was also significantly attenuated by i.p. pretreatment with 7-NI; however, the blockade was not as complete as with L-NMMA or L-NOARG. Cerebella and aorta were removed from vehicle- and 7-NI pretreated rats and assayed for NOS activity by determining the conversion of [14C]L-arginine to [14C]L-citrulline. The 7-NI pretreatment significantly reduced NOS activity in the cerebellum but not the aorta. These findings indicate that the early-phase isoflurane-induced hypotension may involve nNOS as well as eNOS. The nNOS may participate in regulation of isoflurane-induced neuronal release of endogenous opioid peptide, which produces a vasodilation that is dependent on NO derived from an action of eNOS.

An opioid basis for early-phase isoflurane-induced hypotension in rats.

This study was conducted to more clearly delineate the possible role of endogenous opioid receptors and opioid peptides in general anesthesia-associated hypotension in rats. Exposure to 2% isoflurane in oxygen produced a triphasic change in mean arterial pressure (MAP), including an early phase in which MAP fell by -28.4 +/- 2.2%. The magnitude of this early-phase hypotension was attenuated in rats pretreated with intravenous (i.v.) mu-subtype-selective doses of either naloxone or methylnaloxone but not central doses of the selective mu-opioid antagonist beta-funaltrexamine. This early hypotensive phase was also reduced following i.v. pretreatment with antiserum against methionine-enkephalin but not beta-endorphin. These findings suggest that early-phase isoflurane-induced hypotension may be due to activation of peripheral mu-opioid receptors by an endogenous opioid peptide, possibly related to methionine-enkephalin.