Effect of Isoflurane on In Situ Vascular Smooth Muscle Transmembrane Potential in Spontaneous Hypertension
Administration of general anesthetics to patients with chronic hypertension often causes hemodynamic instability that has been attributed in part to a poorly understood increased loss of control of peripheral vascular smooth muscle tone. The purpose of the current study was to determine if such an increased loss occurs in the spontaneously hypertensive (SH) rat neurogenic model of chronic hypertension, as reflected by a greater volatile anesthetic-induced in situ vascular smooth muscle hyperpolarization compared with normotensive Wistar-Kyoto (WKY) rat controls.Methods
Vascular smooth muscle transmembrane potentials (Em) were measured in situ using glass microelectrodes in externalized small mesenteric resistance- and capacitance-regulating blood vessels in 10- to 12-week-old SH and WKY rats before, during, and after administration of 1 minimum alveolar concentration levels (1.5%) of inhaled or 0.60 mM superfused isoflurane. Vascular smooth muscle Em s were also measured in vessels after local sympathetic denervation with superfused 6-hydroxydopamine.Results
Local sympathetic denervation caused a significant hyperpolarization of arterial and venous vascular smooth muscle in SH but not WKY rats. Hyperpolarization induced by either inhaled or superfused isoflurane was significantly greater in innervated than in denervated arterial and venous vascular smooth muscle, particularly in SH rats. In addition, for innervated (but not denervated) arterial and venous vascular smooth muscle, hyperpolarization induced by inhaled (but not superfused) isoflurane was significantly greater in SH than in WKY rats.Conclusions
In the neurogenic SH rat model of human hypertension, a primary mechanism underlying elevated isoflurane-induced vascular smooth muscle hyperpolarization (and reduced vascular smooth muscle tone) in both resistance- and capacitance-regulating blood vessels is a central neural inhibition of excitatory sympathetic input. Peripheral neural and nonneurally mediated hyperpolarization by isoflurane is similar in SH and WKY rat vascular smooth muscles.