| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
 
|
|
|
||
|
|
© 2002 International Anesthesia Research Society
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
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 (Em) 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 · kg-1 · h-1) in sympathetically innervated and locally denervated vessels. Propofol’s effect on Em 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 · kg-1 · 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 · kg-1 · h-1 propofol. Assuming a close inverse correlation between magnitude of VSM Em 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.
IMPLICATIONS: 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.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The IV anesthetic, propofol, produces relatively marked hypotension upon induction of anesthesia in both humans and animals. Such hypotension, which is routinely anticipated and managed by practicing anesthesiologists, has been attributed primarily to both a decrease in systemic peripheral vascular resistance and an increase in vascular capacitance leading to a significant reduction in venous return (1,2).
However, the actions of propofol at the vascular cell and membrane level are not well understood. Propofol-induced vasorelaxation has been demonstrated in vitro in isolated, relatively large, conduit blood vessels (3,4). Biddle et al. (5) have suggested that the peripheral mechanisms for vasorelaxation in such vessels include an inhibition of release of norepinephrine at the vascular neuromuscular junction. However, some of the electrical and mechanical responses of vascular smooth muscle (VSM) to sympathetic neural, physical, and chemical stimuli in these relatively large vessels differ significantly from those of VSM in the small resistance-regulating arteries and capacitance-regulating veins that are more influential in the regulation of blood pressure (6). In addition, small vessel vascular endothelium plays a critical role in the regulation of VSM tone by producing and releasing a variety of vasodilator substances (e.g., endothelium-derived hyperpolarizing factor (EDHF) (7), nitric oxide (NO) (i.e., endothelium-derived relaxing factor [EDRF]) (8), and prostacyclin (PGI2) (9). EDHF causes an endothelium-dependent VSM relaxation that is resistant to EDRF inhibitors (7,10). In small resistance-regulating arteries, EDHF seems to be a major determinant of vascular caliber under normal conditions. Thus, EDHF may be of primary importance in the regulation of peripheral vascular resistance (7).
The relative importance of different mechanisms by which IV propofol alters control of VSM tone in vivo has not been established for the small blood vessels. Active tone in these vessels is inversely correlated with the level of VSM membrane polarization (11–13). Hence, VSM exhibits a tight electromechanical coupling (e.g., a 50% vasorelaxation for a 2.5-mV hyperpolarization) (14). In previous studies, we observed that inhaled anesthetics produce an in situ VSM hyperpolarization in these small vessels. Such hyperpolarization involves both an inhibition of excitatory sympathetic neural input and an action at the level of the VSM cell membrane that includes activation of VSM potassium channels (15,16). Figure 1 illustrates some of the pertinent mechanisms regulating VSM tone in these small blood vessels that may be modulated by inhaled anesthetics to produce hyperpolarization and vasodilatation. The purpose of the present study was to determine whether similar mechanisms underlie the hypotension and vasorelaxation resulting from the IV administration of propofol.
|
In addition, the effect of propofol on in situ endothelium-dependent vasorelaxation in these small vessels was determined by measurement of its effect on acetylcholine (ACh)-induced VSM hyperpolarization.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Animal and Vessel Preparations
The Institutional Animal Care Committee of Toyama Medical and Pharmaceutical University approved the present study. In situ vessels were prepared in male Sprague-Dawley rats with body weights ranging between 250 and 350 g. After random selection for a specific protocol, each animal was sedated with 40 mg/kg intraperitoneal ketamine (Sankyo Pharmaceutical Co., Osaka, Japan) to facilitate weighing and shaving. Subsequently, anesthesia was induced with 20 mg/kg intraperitoneal pentobarbital (Dainabot Pharmaceutical Co., Osaka, Japan). Surgical preparation included femoral arterial and venous cannulations for direct measurement of arterial blood pressure and medication infusion, respectively. In addition, a tracheotomy tube was placed, and ventilation was controlled with a Harvard model 683 ventilator (Harvard Apparatus, South Natick, MA) to maintain end-tidal CO2 between 30 and 40 mm Hg. Basal anesthesia was maintained with pentobarbital (5 mg · kg-1 · h-1).
Each animal was placed on a custom-made, movable microscope stage. A midline laparotomy was performed, through which a loop of terminal ileum with its attached mesentery was externalized to expose small (200–300 µm) branches of mesenteric arteries and veins. These vessels were cleared of perivascular fat without disturbing luminal flow. Surrounding connective tissue was fastened to the silastic rubber floor of a temperature-regulated tissue chamber with small stainless steel pins. A row of smaller stainless steel pins was placed immediately alongside of the arteries and veins to separate them and to minimize pulsations that interfered with transmembrane potential (Em) measurements. The preparation was continuously superfused with a physiologic salt solution (PSS) composed of (mM): NaCl 119, KCl 4.7, MgSO4 1.17, CaCl2 1.6, NaHCO3 24.0, NaHPO4 1.18, and EDTA 0.026 (Sigma Chemical Co., St. Louis, MO). The PSS was maintained at 37°C and aerated with a gas mixture of N2, O2, and CO2 to maintain pH between 7.35 and 7.45, PCO2 between 35 and 45 mm Hg, and PO2 between 75 and 150 mm Hg.
In situ Em Measurements
Single-cell in situ Em measurements were made by advancing 3 M KCl-filled glass micropipettes into VSM cells with a hydraulic micromanipulator (MHO-110; Narashige International, Tokyo, Japan). The potential difference between the intracellular microelectrode and a bath reference electrode was measured by using a microelectrode amplifier (MEZ 8301; Nihon Kohden Co., Tokyo, Japan). Micropipettes with impedances ranging between 40 and 60 M
were pulled from borosilicate glass by using a model P-97 Brown-Flaming micropipette puller (Sutter Instruments Co., Novato, CA). Em and femoral arterial blood pressure were recorded simultaneously by using an RM-6000 polygraph system (Nihon Kohden) and a Superscope 2 digital data acquisition system (GW Instruments, Somerville, MA).
Experimental Protocols
Two experimental series of measurements were performed. In the first, changes in VSM Em were measured in response to slow (10 mg · kg-1 · h-1) and fast (30 mg · kg-1 · h-1) rates of IV infusion of propofol (Zeneca Pharmaceutical Co., Osaka, Japan). Blood concentrations of propofol were measured commercially (BML Co., Tokyo, Japan) from samples taken immediately before the washout periods. Values ranged between 2.8 ± 0.7 and 3.8 ± 1.7 µg/mL during the 10 mg · kg-1 · h-1 infusion rate and between 11.1 ± 3.7 and 13.8 ± 2.7 µg/mL during the 30 mg · kg-1 · h-1 infusion rate. Whole blood concentrations of propofol ranging between 4.5 ± 1.2 µg/mL and 13.6 ± 1.3 µg/mL produce an effective antinociceptive effect in adult male Sprague-Dawley rats (17). In half of the experimental preparations in the first experimental series, sympathetic neural innervation to the vessels was eliminated before Em measurements by local superfusion with 300 µg/mL 6-hydroxydopamine for 20 min. This was followed by a 1-h washout with PSS. Before the administration of 6-hydroxydopamine, the preparation was superfused for 5 min with PSS containing 1 µM phentolamine to block the effect of released catecholamines (18,19). Before all VSM Em measurements in both innervated and denervated vessel preparations, the propofol intralipid vehicle (PharmaciaAB, Stockholm, Sweden) was infused for 1 h at the same concentration and rate as used for the administration of both the small and large doses of propofol. The protocol for each experimental preparation included measurement of arterial blood pressure and VSM Em in small artery and vein just before the administration of propofol (i.e., preinfusion). Subsequently, propofol was administered by IV infusion with a syringe pump (STC-531; Terumo Co., Tokyo, Japan) at either 10 or 30 mg · kg-1 · h-1. After a 30-min equilibration period, measurements were repeated during propofol infusion. Finally, measurements were repeated 1 h after cessation of propofol and its intralipid vehicle infusion (i.e., postinfusion). To evaluate the stability of the experimental preparation as a function of time, VSM Em measurements were made in both the sympathetically innervated and denervated vessel during the total time course of each protocol in the presence of intralipid vehicle infusion.
The second experimental series evaluated the effect of propofol infusion on the in situ VSM hyperpolarization response of the vessels to topical superfusion with ACh (Sigma). Two protocols were used for the study of the effects of propofol infusion on ACh-induced VSM hyperpolarization in the small mesenteric artery. In the first protocol, while continuously infusing intralipid vehicle, VSM Em was measured during vessel superfusion with normal PSS. This measurement was repeated within 3 min after the addition of 3 µM ACh to the superfusate, together with 15 µM NG-nitro-L-arginine-methyl-ester (L-NAME) (Sigma), an inhibitor of endothelium-produced NO, and 5 µM indomethacin (Sigma), an inhibitor of endothelium-produced PGI2. In the second protocol, VSM Ems were measured 30 min after the initiation of a continuous 30 mg · kg-1 · h-1 infusion of propofol, then again within a 3-min time period after the addition of 3 µM ACh, 15 µM L-NAME, and 5 µM indomethacin to the superfusate (with propofol infusion continued). Measurements made within 3 min avoided ACh tachyphylaxis.
All VSM Em and arterial blood pressure data were recorded and analyzed by using a SuperScope 2 software program (GW Instruments). For a specific protocol step in each data table, the listed experimental VSM Em value is the mean ± SD of six to eight average Em values (one average Em value per vessel and one vessel per animal preparation). An average value at a specific protocol step is the numerical average of 5 or more individual VSM cell impalements (each at least 5 s in duration) in a single vessel preparation. For both VSM Em and blood pressure, a one-way analysis of variance with repeated measures (Stat-View program, version 0.5.0; Abacus Concepts, Berkeley, CA) was used to compare mean values between successive steps in each protocol. The significance of differences between mean values was determined by comparison of calculated least-square means at a significance level of P 
0.05. Paired two-tailed t-tests were used to compare respective mean VSM Em and arterial blood pressure values before and during ACh administration. Nonpaired two-tailed t-tests were used to compare the effect of denervation on VSM Em response with propofol and with ACh.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Mean Arterial Blood Pressure (MAP) Responses to Propofol
MAP was measured simultaneously with VSM Em before and after denervation, and in the presence and absence of propofol infusion in each animal preparation. The 30 mg · kg-1 · h-1 propofol infusion rate caused a 12% and 10% reduction in MAP in the animal groups with innervated and denervated vessel preparations, respectively. For each animal preparation, MAP recovered to prepropofol levels after anesthetic washout in the postpropofol period. The 10 mg · kg-1 · h-1 propofol infusion rate did not produce a significant change in MAP in either animal group.
Hyperpolarization of VSM by Propofol
Table 1 lists mean VSM Em values measured before, during, and after 10 and 30 mg · kg-1 · h-1 propofol infusion rates, as well as mean calculated responses to propofol, in both innervated and denervated small mesenteric artery and vein. Propofol significantly hyperpolarized both innervated and denervated arteries and veins at the 30 mg · kg-1 · h-1, but not at the 10 mg · kg-1 · h-1 infusion rate. At 30 mg · kg-1 · h-1, the mean VSM hyperpolarization response to propofol was significantly greater in the innervated compared with the denervated small artery. This was not observed in the small vein.
|
For a time-control study and to determine whether the propofol intralipid vehicle had any effect on VSM Em, mean Em values were measured at each of the three successive time intervals (as in Table 1) but with a simulated large-dose propofol infusion (i.e., infusion of vehicle only). No significant changes in VSM Em were observed during the successive time intervals under these conditions in both innervated and denervated vessel types.
Effect of Propofol on ACh-Induced Hyperpolarization of VSM
In a preliminary study, an ACh concentration-dependent increasing hyperpolarization of VSM was observed in the innervated small artery, but not in the innervated small vein (Fig. 2). In the small artery, a 3-µM concentration of ACh produced a hyperpolarization that was 59% of the value measured during superfusion with 100 µM ACh.
|
The data in Table 2 illustrate that in the innervated small artery, the VSM hyperpolarization response to 3 µM superfused ACh was 6.8 ± 3.4 mV in the absence of propofol infusion. In contrast, the VSM hyperpolarization response to 3 µM superfused ACh was not significantly different from zero in animals already receiving a propofol infusion at 30 mg · kg-1 · h-1 (0.3 ± 2.7 mV).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The first important finding in the present study is that infused propofol, at an antinociceptive blood concentration ranging from 11 to 14 µg/mL, caused a significant in situ VSM hyperpolarization in both sympathetically innervated and locally denervated small mesenteric resistance-regulating arteries and capacitance-regulating veins of the rat. Over its in situ physiologic range (-30 to -50 mV), the magnitude of VSM Em polarization is inversely correlated with active tone in these (and larger) blood vessels (13,14,20). Thus, the VSM hyperpolarization caused by the above blood concentration of propofol in these vessels provides further evidence that a reduction in vascular tone in small resistance- and capacitance-regulating blood vessels contributes significantly to the hypotensive action of this anesthetic in both humans (1,2) and animal models (e.g., rabbit, rat) (3–5,17).
We have previously observed that inhaled anesthetics produce an in situ VSM hyperpolarization of 6–9 mV in sympathetically innervated small mesenteric arteries and 3–9 mV in sympathetically innervated small mesenteric veins. Such hyperpolarization was significantly attenuated (but not eliminated) by local sympathetic denervation (15). This suggested that inhaled anesthetics attenuate both sympathetic neural and nonneural regulation of VSM Em and tone in these vessels. Similar results have been obtained with infused propofol in the present study. In addition, such results are in agreement with results obtained by Biddle et al. (5) demonstrating a propofol-induced attenuation of sympathetic neural control of vascular tone in relatively large conduit vessels (e.g., rat femoral artery). The magnitude of VSM hyperpolarization induced in situ in the sympathetically denervated small mesenteric artery by the 30 mg · kg-1 · h-1 infusion rate of propofol was smaller than in the innervated vessel, but still significant. This suggests that at larger concentrations, propofol-induced attenuation of both sympathetic neural and nonneural mechanisms are involved in the regulation of VSM Em and tone in this vessel. The similar magnitude of VSM hyperpolarization induced in the innervated and denervated vein by this infusion rate of propofol suggests an attenuation primarily of nonneural mechanisms involved in the regulation of VSM Em and tone in this vessel. The reason for such selective action by propofol in the small mesenteric vein is not clear because, in situ, venous active tone is also under sympathetic neural control (13).
Propofol-induced VSM hyperpolarization in small blood vessels may result in a reduction of activator Ca2+ necessary for excitation-contraction coupling. Hyperpolarization resulting from activation of VSM K+ channels reduces Ca2+ influx through voltage-sensitive Ca2+ channels within the VSM membrane as well as the sensitivity of contractile elements (21,22). Siegel et al. (14) have shown that VSM hyperpolarization caused by vasoactive drugs results from activation of K+ channels with consequent closure of voltage-sensitive Ca2+ channels. Previously, we demonstrated that propofol attenuates Ca2+ influx across the mesenteric arterial and venous VSM membrane (3). This supports a propofol-induced activation of K+ channels resulting in coupled hyperpolarization and consequent closure of voltage-sensitive Ca2+ channels as a mechanism of attenuation of VSM tone in small blood vessels.
It is possible that the VSM hyperpolarization induced by propofol in denervated vessels is mediated at least in part by vasodilator factors released from the endothelium (e.g., NO, PGI2, EDHF). Miyawaki et al. (23) reported that propofol inhibits endothelial NO-mediated vasorelaxation in aorta. Park et al. (4) have reported that propofol inhibits EDRF production in aorta and pulmonary artery. It has also been reported that EDHF plays an important role in the regulation of tone in small resistance arteries, whereas NO and the subsequent increase in the cytoplasm concentration of cyclic guanosine 3',5'-monophosphate (cGMP) are predominant in large arteries (7). Studies by others have also shown that in arteries, muscarinic agents, such as ACh, release an unidentified EDHF that is neither PGI2 nor NO (10). Results in the present study demonstrating a concentration-dependent arterial VSM hyperpolarization by ACh in the presence of inhibitors of NO and PGI2 (Fig. 2) also support a vasodilator role for EDHF in these small resistance-regulating vessels. The lack of ACh-induced VSM hyperpolarization in the small mesenteric vein suggests an absence of such a vasodilator role for EDHF in these small capacitance-regulating vessels.
It is of particular interest in the present study that at an infusion rate of 30 mg · kg-1 · h-1 propofol by itself hyperpolarized VSM in the small mesenteric artery, but completely prevented further hyperpolarization by subsequently administered 3 µM ACh (Table 2). These results suggest that propofol, when infused before vessel superfusion with ACh, activates VSM K+ channels either by a direct action at the channel or at a step (or steps) in the adenosine 3',5'-cyclic monophosphate (cAMP) and/or cGMP second messenger pathways leading to their opening (Fig. 1) (20). We have recently demonstrated that an enhanced opening of VSM K+ channels by the volatile anesthetic, isoflurane, involves activation of the cAMP-mediated second messenger pathway (16). If ACh-induced hyperpolarization is mediated by EDHF, these results suggest further that propofol and EDHF act competitively in the second messenger pathways leading to the opening of K+ channels. Substantial evidence based on the effects of K+ channel blockers suggests that EDHF-induced VSM hyperpolarization involves activation of small or intermediate-conductance KCa channels in the VSM membrane (10,20). Propofol may act in a similar manner. In a previous study, we have shown that specific KCa and KATP channel blockers can inhibit volatile anesthetic-mediated VSM hyperpolarization in rat small mesenteric vessels (24).
In summary, the results of the present study demonstrate that in the rat, a 30 mg · kg-1 · h-1 infusion of propofol (which is at an antinociceptive level) attenuates both sympathetic neural and nonneural mechanisms that regulate in situ VSM Em in small mesenteric resistance-regulating arteries and capacitance-regulating veins. At this infusion rate, propofol also blocks the endothelium-dependent arterial hyperpolarization induced by ACh. In the absence of the vasodilator action of NO and PGI2, such actions of ACh are likely mediated by EDHF. The absence of additional VSM hyperpolarization by ACh in the presence of propofol also suggests that propofol and ACh may act competitively in the second messenger pathways leading to the opening of K+ channels in the VSM membrane of the mesenteric resistance arteries.
|
Acknowledgments |
|---|
Supported in part by Grant 0971549 from the Ministry of Education, Science Sports, and Culture of Japan.
The authors thank Dr. Zeljko J. Bosnjak, Professor, and Dr. William J. Stekiel, Professor, Departments of Anesthesiology and Physiology, Medical College of Wisconsin for their critical comments and suggestions concerning this study.
|
Footnotes |
|---|
Presented in part at the annual meeting of the International Anesthesia Society, Orlando, FL, March 1998.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
- Schmidt C, Roosens C, Struys M, et al. Contractility in humans after coronary artery surgery. Anesthesiology 1999; 91: 58–70.[Web of Science][Medline]
-
Muzi M, Berens RA, Kampine JP, Ebert TJ. Venodilation contributes to propofol-mediated hypotension in humans. Anesth Analg 1992; 74: 877–83.
[Abstract/Free Full Text] -
Kamitani K, Yamazaki M, Yukitaka M, et al. Effects of propofol on isolated rabbit mesenteric arteries and veins. Br J Anaesth 1995; 75: 457–61.
[Abstract/Free Full Text] - Park WK, Lynch CD, Johns RA. Effects of propofol and thiopental in isolated rat aorta and pulmonary artery. Anesthesiology 1992; 77: 956–63.[Web of Science][Medline]
- Biddle NL, Gelb AW, Hamilton JT. Propofol differentially attenuates the responses to exogenous and endogenous norepinephrine in the isolated rat femoral artery in vitro. Anesth Analg 1995; 80: 793–9.[Abstract]
- Christensen KL, Mulvany MJ. Mesenteric arcade arteries contribute substantially to vascular resistance in conscious rats. J Vasc Res 1993; 30: 73–9.[Web of Science][Medline]
- Garland CJ, Plane F, Kemp BK, Cocks TM. Endothelium-dependent hyperpolarization: a role in the control of vascular tone. Trends Pharmacol Sci 1995; 16: 23–30.[Medline]
- Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524–6.[Medline]
- Moncada S, Gryglewski R, Bunting S, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 1976; 263: 663–5.[Medline]
- Edwards G, Dora KA, Gardener MJ, et al. K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature 1998; 396: 269–72.[Medline]
-
Nelson MT, Patlak JB, Worley JF, Standen NB. Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. Am J Physiol 1990; 259: C3–18.
[Abstract/Free Full Text] -
Brayden JE, Nelson MT. Regulation of arterial tone by activation of calcium-dependent potassium channels. Science 1992; 256: 532–5.
[Abstract/Free Full Text] - Stekiel WJ. Electrophysiological mechanisms of force development by vascular smooth muscle membrane in hypertension. In: Lee RMKW, ed. Blood vessel changes in hypertension: structure and function. Boca Raton, FL: CRC Press, 1989: 127–70.
- Siegel G, Emden J, Wenzel K, et al. Potassium channel activation in vascular smooth muscle. Adv Exp Med Biol 1992; 311: 53–72.[Medline]
- Yamazaki M, Stekiel TA, Bosnjak ZJ, et al. Effects of volatile anesthetics on in situ vascular muscle transmembrane potential in resistance and capacitance blood vessels. Anesthesiology 1998; 88: 1085–95.[Web of Science][Medline]
- Stekiel TA, Contney SJ, Bosnjak ZJ, et al. Mechanisms of isoflurane-mediated hyperpolarization of vascular smooth muscle in chronically hypertensive and normotensive conditions. Anesthesiology 2001; 94: 496–506.[Web of Science][Medline]
- Shyr MH, Tsai TH, Tan PP, et al. Concentration and regional distribution of propofol in brain and spinal cord during propofol anesthesia in the rat. Neurosci Lett 1995; 184: 212–5.[Web of Science][Medline]
-
Aprigliano O, Hermsmeyer K. In vitro denervation of the portal vein and caudal artery of the rat. J Pharmacol Exp Ther 1976; 198: 568–77.
[Abstract/Free Full Text] - Stekiel TA, Kokita N, Yamazaki M, et al. Effect of isoflurane on in situ vascular smooth muscle transmembrane potential in spontaneous hypertension. Anesthesiology 1999; 91: 207–14.[Web of Science][Medline]
- Standen NB, Quayle JM. K+ channel modulation in arterial smooth muscle. Acta Physiol Scand 1998; 164: 549–57.[Web of Science][Medline]
-
Nelson MT, Quayle JM. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 1995; 268: C799–822.
[Abstract/Free Full Text] -
Yanagisawa T, Okada Y. KCl depolarization increases Ca2+ sensitivity of contractile elements in coronary arterial smooth muscle. Am J Physiol 1994; 267: H614–21.
[Abstract/Free Full Text] - Miyawaki I, Nakamura K, Terasako K, et al. Modification of endothelium-dependent relaxation by propofol, ketamine, and midazolam. Anesth Analg 1995; 81: 474–9.[Abstract]
- Kokita N, Stekiel TA, Yamazaki M, et al. Potassium channel-mediated hyperpolarization of mesenteric vascular smooth muscle by isoflurane. Anesthesiology 1999; 90: 779–88.[Web of Science][Medline]
This article has been cited by other articles:
|
|
 |
|
  A. Stadnicka, S. J. Contney, C. Moreno, D. Weihrauch, Z. J. Bosnjak, R. J. Roman, and T. A. Stekiel 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 J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 727 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. S. Gragasin and S. T. Davidge The effects of propofol on vascular function in mesenteric arteries of the aging rat Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H466 - H474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nagakawa, M. Yamazaki, N. Hatakeyama, and T. A. Stekiel The Mechanisms of Propofol-Mediated Hyperpolarization of In Situ Rat Mesenteric Vascular Smooth Muscle Anesth. Analg., December 1, 2003; 97(6): 1639 - 1645. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
