Mechanisms of Isoflurane-mediated Hyperpolarization of Vascular Smooth Muscle in Chronically Hypertensive and Normotensive Conditions

Abstract

Isoflurane-induced in situ VSM hyperpolarization in denervated, small mesenteric vessels involves a similar activation of KCa and KATP channels and cyclic adenosine monophosphate, but not nitric oxide or cyclic guanosine monophosphate, second messenger pathways in both SHR and WKY. A greater isoflurane-induced VSM hyperpolarization (observed previously in neurally intact SHR vessels) suggests enhanced inhibition of elevated sympathetic neural input as a major mechanism underlying such hyperpolarization (and coupled relaxation) in this neurogenic model of hypertension.

Large-conductance Ca2+-activated K+channel β1-subunit knockout mice are not hypertensive

“…BK channels provide "negative feedback" control of vascular tone as BK channel activation causes hyperpolarization of vascular smooth muscle cell (VSMC) membrane potential, closure of voltage-gated Ca 2ϩ channels, and muscle relaxation. In VSMCs, BK channels are composed of pore-forming ␣-subunits and accessory ␤ 1 -subunits that modulate Ca 2ϩ sensitivity (17,43). The BK channel ␤ 1 -subunit is enriched in VSMC and copurifies with the BK pore-forming ␣-subunit.…”

“…It is unclear if BK ␤ 1 -KO mice also have higher venous tone and contractility, although BK channels were shown to modulate venous capacitance in vivo in pigs (49) and in vitro in some experimental animals (26,43) and humans (14,22,23,37). It has been reported that mean arterial blood pressure (MAP) in BK ␤ 1 -KO mice is elevated ϳ10 -15 mmHg when measured acutely using carotid arterial catheterization (2,32).…”

Mechanism of Differential Cardiovascular Response to Propofol in Dahl Salt-Sensitive, Brown Norway, and Chromosome 13-Substituted Consomic Rat Strains: Role of Large Conductance Ca2+ and Voltage-Activated Potassium Channels

“…To this end, general anesthetics such as isoflurane and pentobarbital were reported to cause vasodilation of peripheral resistance vessels, specifically the small mesenteric arteries and veins, in part by hyperpolarizing the membrane potential of vascular smooth muscle cells (Yamazaki et al, 1998(Yamazaki et al, , 2002Kokita et al, 1999;Stekiel et al, 2001;Nagakawa et al, 2003). This effect was attenuated by blockers of the large conductance Ca 2ϩ and voltage-activated potassium (BK) channels (Kokita et al, 1999;Nagakawa et al, 2003).…”

The effects of anaesthetics on postoperative physiological reactions: a meta‐analysis

“…37 Hemodynamic changes or fewer requirements of vasoactive medication in patients undergoing surgical operations were different from each other using different anaesthesia. 38 Talke et al 41 suggested that infusion of dexmede- tomidine appeared to be beneficial for perioperative hemodynamic management of surgical patients, but the treatment needed greater intraoperative pharmacologic intervention to maintain blood pressure and heart rate. It has been suggested that anaesthetic agents cause immobility by regulating several molecular targets including c-aminobutyric acid A receptors, glutamate receptors, glycine receptors, TREK-1 potassium channels, and Nmethyl-D-aspartate receptor.…”

“…For example, isoflurane causes hyperpolarization of vascular smooth muscle and finally leads to decreased vascular tone via inhibiting Ca 2+ channel or activating K Ca and K ATP channels. 41 Moreover, blood pressure was stimulated by multiple systems, including the rennin-angiotensin system, nitric oxide, and the sympathetic nervous system. A recent study analyzed the effect of four anaesthetics, including pentobarbital, ketaminexylazine, isoflurane, and chloralose-urethane, on the maintenance of blood pressure.…”