scholarly journals Diabetes-associated Alterations in Volatile Anesthetic Actions on Contractile Response to Norepinephrine in Isolated Mesenteric Resistance Arteries

2010 ◽  
Vol 112 (3) ◽  
pp. 595-606 ◽  
Author(s):  
Jun Yoshino ◽  
Takashi Akata ◽  
Kazuhiro Shirozu ◽  
Kaoru Izumi ◽  
Sumio Hoka
Keyword(s):  
Response Curve ◽  
Contractile Response ◽  
Isometric Force ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Calcitonin Gene ◽  
The Right ◽  
Concentration Response Curve

Background Clinical concentrations of volatile anesthetics significantly influence contractile response to the sympathetic neurotransmitter norepinephrine although its precise mechanisms remain unclarified. In this study, we investigated its possible alterations in diabetes, as well as its underlying mechanisms. Methods Isometric force was recorded in small mesenteric arteries from streptozotocin-induced diabetic and age-matched control rats. Results The concentration-response curve for acetylcholine-induced endothelium-dependent relaxation was shifted to the right in diabetic arteries compared with controls. The concentration-response curve for norepinephrine-induced contraction was shifted to the left and upward by both endothelial denudation and diabetic induction. In the presence of endothelium, isoflurane or sevoflurane enhanced norepinephrine-induced contraction in control arteries but not in diabetic arteries; however, in its absence, both anesthetics identically inhibited norepinephrine-induced contraction in both groups. In control arteries, the isoflurane- or sevoflurane-induced enhancement was not affected by adrenomedullin22-52, calcitonin gene-related peptide8-37, 18beta-glycyrrhetinic acid, N-nitro l-arginine, ouabain, Ba, indomethacin, losartan, ketanserin, BQ-123, and BQ-788. Conclusions In diabetes, vascular responses to acetylcholine, norepinephrine, and volatile anesthetics are altered in mesenteric resistance arteries, presumably reflecting endothelial dysfunction and possibly underlying circulatory instability during administration of either anesthetic. Some endothelial mechanisms that are impaired in diabetes would be involved in the anesthetic-induced enhancement of norepinephrine-induced contraction. However, the vasoregulatory mechanism mediated by adrenomedullin, calcitonin gene-related peptide, myoendothelial gap junction, nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, angiotensin II, serotonin, or endothelin-1, all of which have been suggested to be impaired in diabetes, would not be involved in the enhancement.

Comparison of Volatile Anesthetic Actions on Intracellular Calcium Stores of Vascular Smooth Muscle

2001 ◽  
Vol 94 (5) ◽  
pp. 840-850 ◽  
Author(s):  
Takashi Akata ◽  
Mikio Nakashima ◽  
Kaoru Izumi
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Isometric Force ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Mesenteric Arteries ◽  
Systemic Resistance ◽  
Release Mechanism ◽  
Calcium Stores ◽  
Resistance Arteries

Background Volatile anesthetic actions on intracellular Ca2+ stores (ie., sarcoplasmic reticulum [SR]) of vascular smooth muscle have not been fully elucidated. Methods Using isometric force recording method and fura-2 fluorometry, the actions of four volatile anesthetics on SR were studied in isolated endothellum-denuded rat mesenteric arteries. Results Halothane (> or = 3%) and enflurane (> or = 3%), but not isoflurane and sevoflurane, increased the intracellular Ca2+ concentration ([Ca2+]i) in Ca2+-free solution. These Ca2+-releasing actions were eliminated by procaine. When each anesthetic was applied during Ca2+ loading, halothane (> or = 3%) and enflurane (5%), but not isoflurane and sevoflurane, decreased the amount of Ca2+ in the SR. However, if halothane or enflurane was applied with procaine during Ca2+ loading, both anesthetics increased the amount of Ca2+ in the SR. The caffeine-induced increase in [Ca2+], was enhanced in the presence of halothane (> or = 1%), enflurane (> or = 1%), and isoflurane (> or = 3%) but was attenuated in the presence of sevoflurane (> or = 3%). The norepinephrine-induced increase in [Ca2+], was enhanced only in the presence of sevoflurane (> or = 3%). Not all of these anesthetic effects on the [Ca2+]i were parallel with the simultaneously observed anesthetic effects on the force. Conclusions In systemic resistance arteries, the halothane, enflurane, isoflurane, and sevoflurane differentially influence the SR functions. Both halothane and enflurane cause Ca2+ release from the caffeine-sensitive SR. In addition, both anesthetics appear to have a stimulating action on Ca2+ uptake in addition to the Ca2+-releasing action. Halothane, enflurane, and isoflurane all enhance, while sevoflurane attenuates, the Ca2+-induced Ca2+-release mechanism. However, only sevoflurane stimulates the inositol 1,4,5-triphosphate-induced Ca2+ release mechanism. Isoflurane and sevoflurane do not stimulate Ca2+ release or influence Ca2+ uptake.

Mechanisms of Direct Inhibitory Action of Ketamine on Vascular Smooth Muscle in Mesenteric Resistance Arteries

2001 ◽  
Vol 95 (2) ◽  
pp. 452-462 ◽  
Author(s):  
Takashi Akata ◽  
Kaoru Izumi ◽  
Mikio Nakashima
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Direct Evidence ◽  
Contractile Response ◽  
Isometric Force ◽  
Mesenteric Arteries ◽  
Systemic Resistance ◽  
Resistance Arteries ◽  
Fura 2 ◽  
Force Relation

Background Ketamine was previously suggested to relax vascular smooth muscle by reducing the intracellular Ca2+ concentration ([Ca2+]i). However, no direct evidence is available to indicate that ketamine reduces the [Ca2+]i in vascular smooth muscle of systemic resistance arteries. Methods Endothelium-intact or -denuded smooth muscle strips were prepared from rat small mesenteric arteries. Isometric force and [Ca2+]i were measured simultaneously in the fura-2-loaded, endothelium-denuded strips. In some experiments, only isometric force was measured in either the endothelium-intact or beta-escin-treated, endothelium-denuded strips. Results In the endothelium-intact strips, lower concentrations (< or = 30 microm) of ketamine slightly enhanced norepinephrine-induced contraction, whereas higher concentrations (> or = 100 microM) of ketamine inhibited both norepinephrine- and KCl-induced contractions. In the fura-2-loaded strips, ketamine (> or = 100 microM) inhibited the increases in both [Ca2+]i and force induced by either norepinephrine or KCl. Ketamine also inhibited the norepinephrine-induced increase in [Ca2+]i after treatment with ryanodine. In the absence of extracellular Ca2+, ketamine notably inhibited the norepinephrine-induced increase in [Ca2+]i, whereas it only minimally inhibited caffeine-induced increase in [Ca2+]i. Ketamine had little influence on the [Ca2+]i-force relation during force development to stepwise increment of extracellular Ca2+ concentration during either KCl depolarization or norepinephrine stimulation. Ketamine did not affect Ca2+-activated contractions in the beta-escin membrane-permeabilized strips. Conclusions The action of ketamine on contractile response to norepinephrine consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. The direct vasorelaxation is largely a result of reduction of[Ca2+]i in vascular smooth muscle cells. The [Ca2+]i-reducing effects are caused by inhibitions of both voltage-gated Ca2+ influx and norepinephrine-induced Ca2+ release from the intracellular stores.

Role of Endothelium in the Action of Isoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries

2001 ◽  
Vol 95 (4) ◽  
pp. 990-998 ◽  
Author(s):  
Kaoru Izumi ◽  
Takashi Akata ◽  
Shosuke Takahashi
Keyword(s):  
Contractile Response ◽  
Isometric Force ◽  
Direct Action ◽  
Control Level ◽  
Mesenteric Arteries ◽  
Systemic Resistance ◽  
Resistance Arteries ◽  
Mesenteric Resistance Artery

Background It is believed that isoflurane decreases blood pressure predominantly by decreasing systemic vascular resistance with modest myocardial depression. Nevertheless, little information is available regarding the direct action of isoflurane on systemic resistance arteries. Methods With use of the isometric force recording method, the action of isoflurane on contractile response to norepinephrine, a neurotransmitter that plays a central role in sympathetic maintenance of vascular tone in vivo, was investigated in isolated rat small mesenteric arteries. Results In the endothelium-intact strips, the norepinephrine response was initially enhanced after application of isoflurane (2-5%), but it was subsequently almost normalized to the control level during exposure to isoflurane. However, the norepinephrine response was notably inhibited after washout of isoflurane. In the endothelium-denuded strips, the norepinephrine response was gradually inhibited during exposure to isoflurane (> or = 3%), and the inhibition was prolonged after wash-out of isoflurane. The isoflurane-induced enhancement of norepinephrine response was still observed after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of endothelin-1, angiotensin-II, and serotonin receptors; however, it was prevented by superoxide dismutase. Conclusions In isolated mesenteric resistance artery, the action of isoflurane on contractile response to norepinephrine consists of two distinct components: an endothelium-dependent enhancing component and an endothelium-independent inhibitory component. During exposure to isoflurane, the former counteracted the latter, preventing the norepinephrine response from being strongly inhibited. However, only the endothelium-independent component persists after washout of isoflurane, causing prolonged inhibition of the norepinephrine response. Superoxide anions may be involved in the enhanced response to norepinephrine.

The Action of Sevoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries (Part 1)

2000 ◽  
Vol 92 (5) ◽  
pp. 1426-1440 ◽  
Author(s):  
Kaoru Izumi ◽  
Takashi Akata ◽  
Shosuke Takahashi
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Potassium Chloride ◽  
Contractile Response ◽  
Isometric Force ◽  
Direct Action ◽  
Mesenteric Arteries ◽  
Systemic Resistance ◽  
Resistance Arteries ◽  
Endothelin 1

Background The direct action of sevoflurane on systemic resistance arteries is not fully understood. Methods Isometric force was recorded in isolated rat small mesenteric arteries. Results Sevoflurane (2-5%) enhanced contractile response to norepinephrine only in the presence of endothelium, but inhibited it in its absence. Sevoflurane still enhanced the norepinephrine response after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of either endothelin-1 ET-1), angiotensin-II, or sevotonin receptors. Sevoflurane (3-5%) inhibited contractile response to potassium chloride only in the absence of endothelium but did not influence it in its presence. In the endothelium-intact strips, inhibition of the norepinephrine response, which was enhanced during application of sevoflurane, was observed after washout of sevoflurane and persisted for approximately 15 min. In the endothelium-denuded strips, the inhibition of norepinephrine response was similarly prolonged after washout of sevoflurane. However, no significant inhibitions of potassium chloride response were observed after washout of sevoflurane in both the endothelium-intact and the endothelium-denuded strips. Conclusions The action of sevoflurane on norepinephrine contractile response consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. In the presence of endothelium, the former predominates over the latter, enhancing the norepinephrine response. The endothelium-independent component persisted after washout of sevoflurane, leading to prolonged inhibition of the norepinephrine response. The mechanisms behind the sevoflurane-induced inhibition of norepinephrine response are at least in part different from those behind its inhibition of potassium chloride response. Nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin-II, and serotonin are not involved in the vasoconstricting action. (Key words: Halogenated volatile anesthetics; sympathetic nervous system; systemic hypotension; vascular endothelium.)

Effects of Volatile Anesthetics on Acetylcholine-induced Relaxation in the Rabbit Mesenteric Resistance Artery 

1995 ◽  
Vol 82 (1) ◽  
pp. 188-204 ◽  
Author(s):  
Takashi Akata ◽  
Mikio Nakashima ◽  
Kenji Kodama ◽  
Walter A. Boyle ◽  
Shosuke Takahashi
Keyword(s):  
Endothelial Function ◽  
Sodium Nitroprusside ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Mesenteric Arteries ◽  
K Channel ◽  
Resistance Arteries ◽  
Anesthetic Action ◽  
Endothelium Dependent Relaxation

Background Vascular endothelium plays an important role in the regulation of vascular tone. Volatile anesthetics have been shown to attenuate endothelium-mediated relaxation in conductance arteries, such as aorta. However, significant differences in volatile anesthetic pharmacology between these large vessels and the small vessels that regulate systemic vascular resistance and blood flow have been documented, yet little is known about volatile anesthetic action on endothelial function in resistance arteries. Furthermore, endothelium-dependent relaxation mediated by factors other than endothelium-derived relaxing factor (EDRF) has recently been recognized, and there is no information available regarding volatile anesthetic action on non-EDRF-mediated endothelium-dependent relaxation. Methods Employing isometric tension recording and microelectrode methods, the authors first characterized the endothelium-dependent relaxing and hyperpolarizing actions of acetylcholine (ACh) in rabbit small mesenteric arteries, and tested the sensitivities of these actions to EDRF pathway inhibitors and K+ channel blockers. They then examined the effects of the volatile anesthetics isoflurane, enflurane, and sevoflurane on ACh-induced endothelium-dependent relaxation that was sensitive to EDRF inhibitors and that which was resistant to the EDRF inhibitors but sensitive to blockers of ACh-induced hyperpolarization. The effects of the volatile anesthetics on endothelium-independent sodium nitroprusside (SNP)-induced relaxation were also studied. Results Acetylcholine concentration-dependently caused both endothelium-dependent relaxation and hyperpolarization of vascular smooth muscle. The relaxation elicited by low concentrations of ACh (< or = 0.1 microM) was almost completely abolished by the EDRF inhibitors NG-nitro-L-arginine (LNNA), oxyhemoglobin (HbO2), and methylene blue (MB). The relaxation elicited by higher concentrations of ACh (> or = 0.3 microM) was only attenuated by the EDRF inhibitors. The remaining relaxation, as well as the ACh-induced hyperpolarization that was also resistant to EDRF inhibitors, were both specifically blocked by tetraethylammonium (TEA > or = 10 mM). Sodium nitroprusside, a NO donor, produced dose-dependent relaxation, but not hyperpolarization, in the endothelium-denuded (E[-]) strips, and the relaxation was inhibited by MB and HbO2, but not TEA (> or = 10 mM). One MAC isoflurane, enflurane, and sevoflurane inhibited both ACh relaxation that was sensitive to the EDRF inhibitors and the ACh relaxation resistant to the EDRF inhibitors and sensitive to TEA, but not SNP relaxation (in the E[-] strips). An additional finding was that the anesthetics all significantly inhibited norepinephrine (NE) contractions in the presence and absence of the endothelium or after exposure to the EDRF inhibitors. Conclusions The results confirm that ACh has a hyperpolarizing action in rabbit small mesenteric resistance arteries that is independent of EDRF inhibitors but blocked by the K+ channel blocker TEA. The ACh relaxation in these resistance arteries thus appears to consist of distinct EDRF-mediated and hyperpolarization-mediated components. Isoflurane, enflurane, and sevoflurane inhibited both components of the ACh-induced relaxation in these small arteries, indicating a more global depression of endothelial function or ACh signaling in endothelial cells, rather than a specific effect on the EDRF pathway. All these anesthetics exerted vasodilating action in the presence of NE, the primary neurotransmitter of the sympathetic nervous system, which plays a major role in maintaining vasomotor tone in vivo. This strongly indicates that the vasodilating action of these anesthetics probably dominates over their inhibitory action on the EDRF pathway and, presumably, contributes to their known hypotensive effects in vivo. Finally, the vasodilating action of these anesthetics is, at least in part, independent from endothelium.

Contractile effects of cardiac neuropeptides in isolated canine atrial and ventricular muscles

1989 ◽  
Vol 257 (4) ◽  
pp. H1082-H1087 ◽  
Author(s):  
D. F. Rigel ◽  
I. L. Grupp ◽  
A. Balasubramaniam ◽  
G. Grupp
Keyword(s):  
Isometric Force ◽  
Contractile Force ◽  
Adrenergic Blockade ◽  
Canine Heart ◽  
Inotropic Action ◽  
Inotropic Effects ◽  
Calcitonin Gene ◽  
Positive Inotropic Effects ◽  
The Right ◽  
Ventricular Trabeculae

Contractile effects of the cardiac neuropeptides vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and neurotensin (NT) were compared with those of l-isoproterenol (ISO) in isolated canine atrial and ventricular trabeculae muscles stimulated to contract at 1 Hz. In ventricular muscles, ISO, VIP, and PHI augmented developed isometric force by approximately 100%. VIP and PHI were three times and 1/10, respectively, as potent as ISO. VIP also exhibited positive inotropic effects in atrial trabeculae. The contractile responses to VIP were unchanged after beta-adrenergic blockade with nadolol at a concentration (10 microM) that shifted the ISO dose-response curve two to three orders of magnitude to the right. In atrial and ventricular trabeculae, NPY (1 microM) attenuated contractile force by 36 +/- 8 and 30 +/- 4%, respectively. Each peptide also caused comparable increases or decreases in the rate of development of force and the rate of relaxation. CGRP and NT caused no significant changes in developed force in either atrial or ventricular muscles in concentrations up to 1 microM. Our results indicate a potential positive inotropic action of endogenous VIP and PHI and a cardiodepressant effect of endogenous NPY in the canine heart.

Renal microvascular effects of endothelin

1990 ◽  
Vol 259 (2) ◽  
pp. F217-F221 ◽  
Author(s):  
R. M. Edwards ◽  
W. Trizna ◽  
E. H. Ohlstein
Keyword(s):  
Response Curve ◽  
Contractile Response ◽  
Maximum Response ◽  
Lumen Diameter ◽  
Rabbit Kidney ◽  
Significant Shift ◽  
Efferent Arteriole ◽  
Endothelin 1 ◽  
Afferent Arterioles ◽  
Concentration Response Curve

The effects of endothelin 1, 2, and 3 (ET-1, -2, -3) on lumen diameter of individual afferent and efferent arterioles dissected from rabbit kidney were examined. ET-1 produced concentration-dependent and long-lasting decreases in lumen diameter in both arterioles. The 50% maximum response (EC50) values were 1.4 +/- 0.41 and 0.9 +/- 0.65 nM for afferent and efferent arterioles, respectively. In afferent arterioles, ET-2 produced decreases in lumen diameter (EC50 = 3.3 +/- 1.75 nM) that were indistinguishable from ET-1. However, ET-3 was considerably less potent (EC50 = 21.9 +/- 6.0 nM, P less than 0.05) than ET-1 or ET-2. Similar results were obtained in the efferent arteriole in which the EC50 for ET-2 (0.25 +/- 0.1 nM) was similar to ET-1, but ET-3 was significantly less potent (EC50 = 2.6 +/- 0.4 nM, P less than 0.05). Nicardipine (0.01-1 microM) produced concentration-dependent shifts in the ET-1 concentration-response curve in afferent arterioles. Verapamil (1 microM) also caused a significant shift in the ET-1 response curve. The contractile response to ET-1 was significantly more sensitive to nicardipine than was the response to norepinephrine. In contrast, the response of efferent arterioles to ET-1 and norepinephrine was unaffected by nicardipine or verapamil. The results demonstrate that ETs are potent vasoconstrictors of both the pre- and postglomerular microvasculature and may play a role in the regulation of renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Existence of two types of postjunctional α-adrenoceptors in the isolated canine internal carotid artery

1988 ◽  
Vol 66 (5) ◽  
pp. 655-659 ◽  
Author(s):  
Yasuaki Kawai ◽  
Shigeaki Kobayashi ◽  
Toshio Ohhashi
Keyword(s):  
Response Curve ◽  
Carotid Arteries ◽  
Internal Carotid ◽  
The Other ◽  
Low Concentrations ◽  
Selective Agonists ◽  
High Concentrations ◽  
The Right ◽  
Internal Carotid Arteries ◽  
Concentration Response Curve

The pharmacological characteristics of postjunctional α-adrenoceptors in isolated canine internal carotid arteries were investigated by the use of selective agonists and antagonists for α1 and α2-adrenoceptors. Norepinephrine, phenylephrine, and xylazine caused concentration-dependent contractions in the helical strips. The contraction induced by 10−4 M xylazine was significantly smaller than that produced by 10−4 M norepinephrine or 10−4 M phenylephrine. The contraction induced by 10−4 M phenylephrine was almost the same value as that induced by 10−4 M norepinephrine. Phentolamine (10−8 and 10−7 M) caused a parallel shift to the right of the concentration–response curve to norepinephrine. The contractile responses to low concentrations of norepinephrine were significantly suppressed by pretreatment with an α2-antagonist such as yohimbine (10−9 and 10−8 M) or DG 5128(10−7 and 10−6 M). On the other hand, the responses to higher concentrations of norepinephrine were mainly reduced by low concentrations of an α1-antagonist, prazosin (3 × 10−10 and 3 × 10−9 M). These results suggest that both α1- and α2-adrenoceptors are located on the plasma membrane of smooth muscle cells in canine internal carotid arteries and that the norepinephrine-induced contractions at low and high concentrations are mainly mediated by activation of α2- and α1-adrenoceptors, respectively.

Abstract P277: β-arrestin-2-mediated Vasodilatation In Mouse Mesenteric Arteries

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Victor M Pulgar ◽  
Krisztian Toth
Keyword(s):  
Vascular Function ◽  
Isometric Force ◽  
Mesenteric Arteries ◽  
Maximal Response ◽  
Lower Sensitivity ◽  
Dependent Manner ◽  
Resistance Arteries ◽  
Response Curves ◽  
Vascular Dilatation

As part of GPCRs-dependent signaling, β -arrestin-2 has been shown to stimulate eNOS activity and thus has the potential to modulate vascular function. We hypothesized that the absence of β -arrestin-2 would alter vascular dilatation and contraction in resistance arteries. We tested acetylcholine (ACh)-dependent relaxation and phenylephrine (PE)-dependent contraction in mouse mesenteric arteries isolated from 3-mo old male C57Bl6 (WT, n=5) and β -arrestin-2 KO ( βarr2 -/- , n=5) mice. Segments were mounted in a Wire Myograph (DMT) for determination of isometric force; vessels studied included intact, without endothelium, or pre-incubated with L-NAME (10 -4 M). Dose-response curves were performed for ACh (10 -10 -10 -4.5 M) and PE (10 -10 -10 -4.5 M). Data were acquired using a PowerLab (ADInstruments) system. Maximal response to ACh (ACh MAX ) was expressed as maximal relaxation after pre-constriction, maximal response to PE (PE MAX ) as % of contraction to 75mM KCl (%K MAX ), and sensitivity as pD 2 (-Log[EC 50 ]). Data were analyzed using Prism (GraphPad). After pre-constriction (PE, 3x10 -6 M), arteries from βarr2 -/- mice presented similar ACh MAX (79±6 vs. 82±6, p>0.05) and lower sensitivity to ACh compared to WT (6.66±0.2 vs. 7.12±0.1, p<0.05). The sensitivity of the contraction to PE was increased in βarr2 -/- arteries (6.4±0.2 vs. 6.04±0.1, p<0.05), with no changes in PE MAX . Differences in vasodilation and contraction were abolished in arteries without endothelium and in arteries pre-incubated with L-NAME. We conclude that the absence of β -arrestin-2 induces a pro-contractile phenotype in an endothelium- and nitric oxide-dependent manner in mouse resistance arteries.

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