General Anesthetics and Vascular Smooth Muscle

Abstract

General anesthetics threaten cardiovascular stability by causing changes in cardiac function, vascular reactivity, and cardiovascular reflexes and significantly alter distribution of cardiac output to various organs. Their overall impact is often systemic hypotension, which is attributable to myocardial depression, peripheral vasodilation, and attenuated sympathetic nervous system activity. However, one could be more causative than the others, depending on anesthetic agents and cardiovascular factors inherent in patients (e.g., coexisting heart disease). It is generally believed that most general anesthetics attenuate sympathetic nervous system outflow from the central nervous system, thereby decreasing vascular resistance in peripheral circulations. Indeed, in previous in vivo studies, during administration of various general anesthetics, vascular resistance was decreased in most peripheral circulations; however, it was unaffected or increased in some peripheral circulations. General anesthetics may act directly on vascular smooth muscle and/or endothelial cells in various vascular beds, influencing total peripheral and/or regional vascular resistance, and hence organ blood flow. This article reviews previously reported direct (i.e., nonneural) vascular actions of general anesthetics and discusses their underlying mechanisms, their in vivo relevance, and the future of research for general anesthetic vascular pharmacology.

Differential Effects of Intravenous Anesthetics on PDGF-BB-Induced Vascular Smooth Muscle Cell Migration

“…Intravenous anesthetics are firmly established to have direct effects on vascular smooth muscle cells (VSMCs), resulting in modulation of blood pressure. For example, ketamine or midazolam reduces both intracellular Ca 2+ concentration ([Ca 2+ ]i) and myofilament Ca 2+ sensitivity, which leads to vasorelaxation [2]. Propofol reduces [Ca 2+ ]i via the protein kinase C (PKC)-dependent pathway, increasing guanosine 3', 5'-cyclic monophosphate (cGMP) or hyperpolarization of K + channel [2].…”

“…For example, ketamine or midazolam reduces both intracellular Ca 2+ concentration ([Ca 2+ ]i) and myofilament Ca 2+ sensitivity, which leads to vasorelaxation [2]. Propofol reduces [Ca 2+ ]i via the protein kinase C (PKC)-dependent pathway, increasing guanosine 3', 5'-cyclic monophosphate (cGMP) or hyperpolarization of K + channel [2]. In our previous study [3], we have demonstrated that propofol inhibits endothelin-1-induced Ca 2+ influx and phosphoinositide-hydrolysis in VSMCs and the suppressive effect is exerted at the point between the receptors and heterotrimeric GTP-binding protein.…”

Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

“…The calcium-dependent mechanism for vascular smooth muscle contraction is associated with a change in the concentration of cytosolic free calcium (Akata 2007). Calcium is mobilized from the sarcoplasmic reticulum and (or) the extracellular space to increase the cytosolic free calcium concentration, which stimulates the binding of calcium to calmodulin, leading to vasoconstriction (Akata 2007).…”

Effect of propofol on human fetal placental circulation

“…Indeed, earlier studies have shown that propofol inhibited extracellular Ca 2+ -dependent responses to PGF 2a and KCL thereby suggesting that it may also inhibit receptor-operated calcium channel and voltage-operated calcium channel activities. 33 In contrast to its actions on KCl, BK, and PGF 2a , propofol does not reduce the vasoconstrictive effect of Ang II on human fetal placental circulation. This demonstrates that the mechanism of vasoconstrictor action of Ang II in the human fetal placental circulation is different at least in part from those of KCl, BK, and PGF 2a .…”

“…35 Finally, general anesthetics have been proposed to influence the myofilament Ca 2+ sensitivity of vascular smooth muscle cells in either the absence or presence of receptor stimulation. However, the underlying mechanisms are not well understood, 33 and possible alterations in myofilament Ca 2+ sensitivity by propofol in fetal placental circulation are not known.…”