Mechanisms of L‐N<sup>G</sup> nitroarginine/indomethacin‐resistant relaxation in bovine and porcine coronary arteries

Graier, Wolfgang F.; Holzmann, S.; Hoebel, Bernhard G.; Kukovetz, W. R.; Kostner, Gert M.

doi:10.1111/j.1476-5381.1996.tb16020.x

Cited by 34 publications

(25 citation statements)

References 31 publications

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“…A similar role for CTX and apamin-sensitive potassium channels in vasorelaxation to BK and acetylcholine has been demonstrated in a variety of other models. 26,30 These findings are consistent with our observations that both BK Ca and SK Ca K ϩ channels contribute to BK-induced vasodilation in human coronary arterioles.…”

Section: Figure 9 Effect Of Ksupporting

confidence: 91%

Human Coronary Arteriolar Dilation to Bradykinin Depends on Membrane Hyperpolarization

1999

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Background-Kϩ channel activation in vascular smooth muscle cells (VSMCs) plays a key role in regulating vascular tone. It has been proposed that endothelium-derived hyperpolarizing factor (EDHF) contributes to microvascular dilation more than nitric oxide (NO) does. Whether hyperpolarization is important for coronary arteriolar dilation in humans is not known. Bradykinin (BK), an endogenous vasoactive substance, is released from ischemic myocardium and regulates coronary resistance. Therefore, we tested the effects of inhibiting NO synthase, cyclooxygenase, and K ϩ channels on the changes in diameter and membrane potential (Em) in response to BK in isolated human coronary microvessels. Methods and Results-Arterioles (97Ϯ4 m; nϭ120) dissected from human right atrial appendages (nϭ78) were cannulated at a distending pressure of 60 mm Hg and zero flow. Changes in vessel diameter (video microscopy) and VSMC Em (glass microelectrodes) were measured simultaneously. In vessels constricted and depolarized (Em; Ϫ50Ϯ3 to Ϫ28Ϯ2 mV) with endothelin-1 (ET), dilation to BK was associated with greater membrane hyperpolarization (Ϫ48Ϯ3 mV at 10 Ϫ6 mol/L) than dilation to sodium nitroprusside (SNP) (Ϫ34Ϯ2 mV at 10 Ϫ4 mol/L) for similar degrees of dilation. Treatment with N

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Section: Figure 9 Effect Of Ksupporting

confidence: 91%

Human Coronary Arteriolar Dilation to Bradykinin Depends on Membrane Hyperpolarization

1999

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“…In some statistical significance, while in coronary microvessels the studies, however, several cytochrome P450 inhibitors have largest part of the hyperpolarization persists in the combeen shown to be without specific effect on the bradykininbined presence of indomethacin, L-NA and HbO. This induced EDHF-mediated relaxations in the pig coronary directly indicates that, although residual NO might be artery [56][57][58]. Moreover, some of these cytochrome P450 present in some conditions in which only NOS inhibitors 1 inhibitors directly affect K channel activation [59,60], and no additional NO scavengers are used, a separate thereby preventing the action of EDHF.…”

Section: Atpmentioning

confidence: 92%

EDHF and residual NO: different factors

Vanheel

2000

Cardiovascular Research

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See article by Ge et al. [61] ( pages 547 -556) in thishyperpolarization in the rat aorta and pulmonary artery [4], issue.the rabbit femoral artery [5] or the dog mesenteric artery [6]. Therefore, the existence of another relaxing factor, unrelated to NO and prostanoids, was proposed to contrib-1. Introduction ute to endothelium-mediated relaxations [4,7,8]. This factor has been called endothelium derived hyperpolarizing The endothelium plays a pivotal role in the control of factor (EDHF). Later reports showed that inhibition of vascular tone and blood pressure. In response to a variety NOS had no effect on endothelium-dependent hyperpolariof physiological stimuli, such as bradykinin, acetylcholine, zation in the coronary artery [9,10], the rat mesenteric histamine, substance P, shear stress and pulsatile stretch, artery [11] and femoral vein [12]. The importance of endothelial cells release vasodilator substances. Those EDHF in vasorelaxation was described to depend on the include prostacyclin [1] and endothelium-derived relaxing stimulus, the kind of vascular bed and the species under factor (EDRF) [2]. The latter has been identified as nitric study. In several vascular beds, it has been shown that oxide (NO) [3]. This labile compound is continuously endothelium-dependent EDHF-mediated relaxations insynthesized from L-arginine by the nitric oxide synthase crease with decreasing size of the vessel [13]. Up to now, (NOS) enzyme constitutively expressed in the endothelial however, the chemical nature of this factor remains cell. It acts by direct stimulation of the soluble guanylyl elusive. Among possible candidates are epoxyeicosatcyclase in vascular smooth muscle cells. Since the elucidarienoic acids (EETs) [14], which are cytochrome P450-tion of the biosynthesis of NO, L-arginine analogues such derived metabolites of arachidonic acid, arachidonyl-etha-and N -nitro-Lnolamide or a related cannabinoid [15], or potassium ions arginine (L-NA) and its methyl ester (L-NAME) have been [16]. Recent evidence suggests that an EDHF diffuses to used as inhibitors of NOS to assess the contribution of the the vascular smooth muscle cells via heterocellular gap NO / cGMP pathway in endothelium-dependent responses.junctions [17]. In the presence of inhibitors of both cyclo-oxygenase and NOS, residual endothelium-dependent relaxations were observed in a variety of preparations. Moreover, 2. Nitric oxide causes hyperpolarization direct measurements of the smooth muscle membrane potential showed agonist-induced hyperpolarizations which During the past decade, the existence of a separate disappeared after removal of the endothelium. Hyperpo-EDHF has been repeatedly challenged. Thus, while earlier larization of the vascular smooth muscle cells is known to studies had shown that NO itself did not influence the cause relaxation by decreasing the open-probability of resting membrane potential of vascular smooth muscle voltage-dependent calcium channels and by interfering cells [6,18], a key observation questioning the existence of w...

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“…EETs relax coronary arteries [73,74], activate Ca 2ϩ -dependent K ϩ channels in coronary artery smooth-muscle cells [73,75,76], and the hydration product of 11,12-EET (i.e., 11,12-DHET) inhibits cardiac Na ϩ /K ϩ -ATPase [77]. In addition, 19-HETE is vasoactive [78,79].…”

Section: A Heartmentioning

confidence: 99%

P450 Subfamily Cyp2j and Their Role in the Bioactivation of Arachidonic Acid in Extrahepatic Tissues*

Scarborough

et al. 1999

Drug Metabolism Reviews

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Mechanisms of L‐N^G nitroarginine/indomethacin‐resistant relaxation in bovine and porcine coronary arteries

Cited by 34 publications

References 31 publications

Human Coronary Arteriolar Dilation to Bradykinin Depends on Membrane Hyperpolarization

Human Coronary Arteriolar Dilation to Bradykinin Depends on Membrane Hyperpolarization

EDHF and residual NO: different factors

P450 Subfamily Cyp2j and Their Role in the Bioactivation of Arachidonic Acid in Extrahepatic Tissues*

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Mechanisms of L‐NG nitroarginine/indomethacin‐resistant relaxation in bovine and porcine coronary arteries

Cited by 34 publications

References 31 publications

Human Coronary Arteriolar Dilation to Bradykinin Depends on Membrane Hyperpolarization

Human Coronary Arteriolar Dilation to Bradykinin Depends on Membrane Hyperpolarization

EDHF and residual NO: different factors

P450 Subfamily Cyp2j and Their Role in the Bioactivation of Arachidonic Acid in Extrahepatic Tissues*

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Mechanisms of L‐N^G nitroarginine/indomethacin‐resistant relaxation in bovine and porcine coronary arteries