The effects of propofol on neural and endothelial control of in situ rat mesenteric vascular smooth muscle transmembrane potentials.

Abstract

We indirectly assessed the in vivo effect of propofol on sympathetic neural and endothelial control of vascular smooth muscle (VSM) tone in Sprague-Dawley rats by measurement of in situ responses of VSM transmembrane potential (E(m)) in intact, small mesenteric arteries and veins superfused with physiologic salt solution. Measurements were made before, during, and after propofol infusion (10 and 30 mg x kg(-1) x h(-1)) in sympathetically innervated and locally denervated vessels. Propofol's effect on E(m) response to superfusion with acetylcholine (ACh), in physiologic salt solution also containing NG-nitro-L-arginine-methyl-ester and indomethacin, was determined in innervated vessels. At 30 mg x kg(-1) x h(-1), propofol caused greater arterial VSM hyperpolarization in innervated compared with denervated vessels (4.8 +/- 2.0 mV versus 2.8 +/- 1.5 mV, respectively). ACh hyperpolarized arterial, but not venous, VSM (e.g., 11.7 +/- 2.4 mV at 10(-4) M). ACh-induced hyperpolarization was eliminated by 30 mg x kg(-1) x h(-1) propofol. Assuming a close inverse correlation between magnitude of VSM E(m) and contractile force, these results suggest that propofol attenuates both sympathetic neural and nonneural regulation of VSM tone. They also suggest that propofol and ACh may act competitively in the second messenger cascade regulating VSM K+ channel activity in mesenteric resistance arteries. Vascular smooth muscle (VSM) contractile force responses to the IV anesthetic, propofol, were indirectly assessed by VSM membrane potential changes to clarify the mechanisms underlying attenuation of peripheral vascular control of arterial blood pressure. Results indicate that propofol-induced VSM membrane hyperpolarization and coupled reduction of VSM contractile force underlie such attenuation.