ATP-sensitive K+ channels in rat aorta and brain microvascular endothelial cells

Janigro, Damir; West, G. Alexander; Gordon, Ellen L.; Winn, H. Richard

doi:10.1152/ajpcell.1993.265.3.c812

Cited by 136 publications

(80 citation statements)

References 23 publications

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“…The presence of ATP-sensitive K + channels has been described in endothelium from rat aorta and cerebral microvessels, and activation of these channels on endothelium may be involved in release of vasoactive substances such as EDRF or endothelium-derived hyperpolarization factor. 44 Activation of ATP-sensitive K + channels mediates coronary vasodilation during decreases in perfusion pressure within the autoregulatory range 19 and dilation of collateral and noncollateral vessels during ischemia. 19 ' 2t) During both decreases in perfusion pressure and after coronary occlusion, dilation of arterioles and collaterals less than 100 /im in diameter was inhibited by the ATP-sensitive K + channel inhibitor glibenclamide.…”

Section: Effect Of Atherosclerosis On Coronary Responses To Aprikalimmentioning

confidence: 99%

Enhanced coronary vasoconstrictive response to serotonin subsides after removal of dietary cholesterol in atherosclerotic monkeys.

Lamping

Piegors

Benzuly

et al. 1994

Arterioscler Thromb

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Constriction in response to serotonin is enhanced in the coronary arteries of atherosclerotic monkeys. The main objective of the present study was to determine whether abnormal responses to serotonin in atherosclerosis are reversed following removal of dietary cholesterol. In addition, we examined the effect of an atherogenic diet and reduction in dietary cholesterol on vascular responses to activation of ATP-sensitive K + channels with aprikalim. Diameters of small coronary arteries were measured on the epicardial surface of the left ventricle in vivo by using stroboscopic illumination synchronized to the heart cycle to visually freeze the motion of the heart. Diameters were measured with a microscope-video system during topical application of two vasoconstrictor agonists, serotonin and the thromboxane mimetic U46619, and the vasodilator agonists aprikalim and nitroprusside. Responses V ascular responsiveness to several agonists is altered by atherosclerosis, 17 and coronary vasoconstrictor responses to serotonin are augmented in patients with atherosclerosis or unstable angina. 56 Coronary microvessels relax in response to serotonin in normal monkeys and constrict in atherosclerotic animals.8 Thus, vasomotor abnormalities of atherosclerosis extend to the coronary microcirculation despite an absence of morphological evidence of disease.8 " A critical question is whether abnormal vascular responses in the atherosclerotic coronary circulation can be restored to normal by reducing dietary cholesterol. Reduction of dietary cholesterol reduces the intimal area of arteries as lipids are reabsorbed from the vessel wall.1214 Fibrosis progresses within the artery, however, so that maximal vasodilator responses do not improve consistently. 13 Nevertheless, studies in the hindlimb and cerebral circulation suggest improvement in vascular function after regression of atherosclerosis, with restoration of endothelium-dependent relaxation 15 and reduction in abnormal vasoconstriction in response to serotonin. 1617 It is unclear whether reductions in dietary cholesterol restore vascular reactivity of the coronary circulation to normal. The major objective of the present study was to determine whether reduction were compared in normal (n=9), atherosclerotic (n=14; highcholesterol diet), and regression (n=8; high-cholesterol diet followed by normal diet) monkeys. Constriction of coronary arteries in response to serotonin was enhanced in monkeys on an atherogenic diet and was normal in regression monkeys. Vasoconstriction in response to U46619 and vasodilation in response to nitroprusside and aprikalim were not altered by atherosclerosis. Thus, abnormal vascular responses to serotonin in small coronary arteries of atherosclerotic monkeys without morphological evidence of disease can be reversed to normal by reducing dietary cholesterol. (Arterioscler Thromb. 1994;14:951-957.) Key Words • serotonin • U46619 • aprikalim • nitroprusside • coronary resistance of dietary cholesterol in atherosclerotic monkeys abolishes v...

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Section: Effect Of Atherosclerosis On Coronary Responses To Aprikalimmentioning

confidence: 99%

Enhanced coronary vasoconstrictive response to serotonin subsides after removal of dietary cholesterol in atherosclerotic monkeys.

Lamping

Piegors

Benzuly

et al. 1994

Arterioscler Thromb

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“…For example, isolated penetrating arterioles are capable of reacting to changes in pH and to a number of chemicals, compounds and peptides [e.g., NO (Furchgott and Zawadzki, 1980), adenosine (Meno et al, 1993), ATP (Dietrich et al, 1996;Janigro et al, 1993), K + (Horiuchi et al, 2002;Kuffler and Potter, 1964), VIP ]. Some of these substances exert their effects selectively with luminal or abluminal application.…”

Section: Physiology Of the Pial And Penetrating Arterial Circulamentioning

confidence: 99%

Regulation of cerebral vasculature in normal and ischemic brain

et al. 2008

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In the present review, we focus on the regulation of cerebral blood flow (CBF) and cerebral vasculature in the normal and ischemic brain, with a special emphasis on the arterial microcirculation of the brain: the pial and penetrating vessels. I. BackgroundThe cerebral circulation can be divided into categories based on a number of criteria. For example, vessel size can be utilized to divide the brain circulation into the macro-circulation and the microcirculation. On the arterial side, the former begins in the neck and extends to pial arteries. The microcirculation consists of the pial and penetrating arterioles, the capillaries and the venules. Within the arterial circulation, the major function of the macro-circulation is conductance of blood whereas the principal activity of the arterial component of the microcirculation is regulation of flow. Although the capillaries and venules are a significant contributor to cerebrovascular resistance, their role in regulation of flow is minimal under physiologic conditions. In addition to size, vessel location can be used to characterize the brain circulation. Thus, the brain vasculature can be divided in relation to the parenchyma into an extrinsic and an intrinsic component. The former encompasses the large conductance vessels (i.e., the macrocirculation) plus the pial circulation, whereas the latter consists of the intracerebral circulation composed of small arterioles, capillaries and venules. Penetrating arterioles represent the transition from the extrinsic to the intrinsic system. Clearly these two systems differ in regard to a number of features, such as proximity to the parenchyma, influence of neuronal and astrocytic activity, and presence and origin of innervation. However, despite these differences, both the extrinsic and intrinsic components of the cerebral circulation have an integrated response to cerebral challenges: co-dependency is the norm under physiologic and most pathologic conditions.

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“…The endothelial cells modulate the activity of smooth muscle cells by producing vasodilators, such as prostacyclin and nitric oxide (NO), and vasoconstrictors, such as thromboxane A2 and endothelin-1 (ET-1). Endothelial dysfunction is a condition in which the physiological balance between vasodilator stimuli and vasoconstrictor substances is shifted towards the latter (4,5); this state has been clearly shown in PH (6). NO has gained attention as a significant mediator of PH by virtue of its ability to produce factors that regulate blood flow and vascular tone.…”

Section: Introductionmentioning

confidence: 99%

“…The Ca 2+ influx in endothelial cells is controlled by the membrane potential (26). K ATP channels are present in endothelial cells of the vascular system (6,27) and are responsible for maintaining the resting potential of endothelial cells and modulating the release of vasoactive compounds. Thus, K ATP channels may play a key role in generating the electrical activity of endothelial cells and have profound effects on endothelial function.…”

mentioning

confidence: 99%

“…Thus, K ATP channels may play a key role in generating the electrical activity of endothelial cells and have profound effects on endothelial function. In fact, pinacidil, a K ATP channel opener, has been shown to cause an increase of Ca 2+ influx in rat aorta and brain microvascular endothelial cells (6). Iptakalim, a new compound of the potassium channel opener class, is a promising drug undergoing Phase II clinical trials to treat pulmonary hypertension (28).…”

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confidence: 99%

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Iptakalim rescues human pulmonary artery endothelial cells from hypoxia-induced nitric oxide system dysfunction

Feng¹,

Zuo

Wang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. The aim of this study was to assess whether hypoxia inhibits endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production, and whether iptakalim may rescue human pulmonary artery endothelial cells (HPAECs) from hypoxia-induced NO system dysfunction. HPAECs were cultured under hypoxic conditions in the absence or presence of 0.1, 10 and 1,000 µM iptakalim or the combination of 10 µM iptakalim and 1, 10 and 100 µM glibenclamide for 24 h, and the eNOS activity and NO levels were measured in the conditioned medium from the HPAEC cultures. The eNOS activity and NO levels were reduced significantly in the conditioned medium from HPAEC cultures under hypoxic conditions. Pre-treatment with 10 µM iptakalim normalized the reduction of the eNOS activity and NO levels caused by hypoxia in the conditioned medium from HPAEC cultures. Iptakalim raised the eNOS activity and NO levels under hypoxic conditions, but was blocked by the K ATP channel blocker, glibenclamide. Our results indicate that hypoxia impairs NO system function, whereas the ATP-sensitive K + channel opener, iptakalim, may rescue HPAECs from hypoxia-induced NO system dysfunction.

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ATP-sensitive K+ channels in rat aorta and brain microvascular endothelial cells

Cited by 136 publications

References 23 publications

Enhanced coronary vasoconstrictive response to serotonin subsides after removal of dietary cholesterol in atherosclerotic monkeys.

Enhanced coronary vasoconstrictive response to serotonin subsides after removal of dietary cholesterol in atherosclerotic monkeys.

Regulation of cerebral vasculature in normal and ischemic brain

Iptakalim rescues human pulmonary artery endothelial cells from hypoxia-induced nitric oxide system dysfunction

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