Decreased endothelial size and connexin expression in rat caudal arteries during hypertension

Rummery, Nicole M.; McKenzie, Katja U.S.; Whitworth, Judith A.; Hill, Caryl E.

doi:10.1097/00004872-200202000-00014

Cited by 50 publications

(54 citation statements)

References 26 publications

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“…A number of pathologies in which intercellular communication is disrupted are known where the gap-junction proteins Cxs are modified (11,21,27,28,31,41,53). In the present report, we first demonstrate that Cx37 and Cx40 protein expression were significantly lowered in coronary ECs isolated from diabetic mice when compared with ECs from control (Fig.…”

Section: Discussionsupporting

confidence: 59%

“…The Cx40-knockout mice are hypertensive (11), whereas polymorphisms in the promoter of Cx40 gene have been shown to associate with increased risk of hypertension in patients (21). Furthermore, in hypertensive rats, Cx40 protein expression is decreased in ECs (28,41) [but not in the kidney (24) and the cardiomyocyte (2)]. These data suggest that Cx40 in ECs may play an important role in the development of hypertension; however, the role of Cx40 in coronary endothelial dysfunction in diabetes is unexplored.…”

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confidence: 99%

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Downregulation of connexin40 is associated with coronary endothelial cell dysfunction in streptozotocin-induced diabetic mice

Platoshyn

Suárez

Yuan

et al. 2008

American Journal of Physiology-Cell Physiology

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Dillmann WH. Downregulation of connexin40 is associated with coronary endothelial cell dysfunction in streptozotocin-induced diabetic mice. Am J Physiol Cell Physiol 295: C221-C230, 2008. First published May 7, 2008 doi:10.1152/ajpcell.00433.2007.-Vascular endothelial cells (ECs) play a major role in regulating vascular tone and in revascularization. There is increasing evidence showing endothelial dysfunction in diabetes, although little is known about the contribution of connexins (Cxs) to vascular complications in the diabetic heart. This study was designed to investigate the role of Cxs in coronary endothelial dysfunction in diabetic mice. Coronary ECs isolated from diabetic mice exhibit lowered protein levels of Cx37 and Cx40 (but not Cx43) and a loss of gap junction intercellular communication (GJIC). Vasodilatation induced by the assumed contribution of ECdependent hyperpolarization was significantly reduced in the diabetic coronary artery (CA). Cx40-specific inhibitory peptide 40 GAP27 strongly attenuated endothelium-dependent relaxation in diabetic CA at the concentration that does not affect the relaxation in control CA, suggesting that the total amount of Cx40 is lower in diabetic CA than in control CA. In diabetic mice, coronary capillary density was significantly decreased in vivo. In vitro, GJIC inhibitor attenuated the ability of EC capillary network formation. High-glucose treatment caused a decrease in Cx40 protein expression in ECs and impaired endothelial capillary network formation, which was restored by Cx40 overexpression. Furthermore, we found that the hyperglycemia-induced decrease in Cx40 was associated with inhibited protein expression of Sp1, a transcriptional factor that regulates Cx40 expression. These data suggest that downregulation of Cx40 protein expression and resultant inhibition of GJIC contribute to coronary vascular dysfunction in diabetes.

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Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 99%

Downregulation of connexin40 is associated with coronary endothelial cell dysfunction in streptozotocin-induced diabetic mice

Platoshyn

Suárez

Yuan

et al. 2008

American Journal of Physiology-Cell Physiology

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“…The number of myoendothelial gap junctions per endothelial cell was determined from the surface area of the arterial segment at the level of the internal elastic lamina, the surface area of endothelial cells, and the number of myoendothelial gap junctions present in this region. Endothelial cell size was determined from immunohistochemical preparations, as described previously (43).…”

Section: Methodsmentioning

confidence: 99%

“…Charybdotoxin was dissolved in PBS containing 0.1% BSA. Cx-mimetic peptides 40 Gap27 and 37,43 Gap27 (SRPTEKNVFIV, SRPTEKTIFII, respectively) were synthesized by the Australian Cancer Research Foundation Biomolecular Resource Facility, John Curtin School of Medical Research; purity Ͼ97%. All other drugs were made up as ϫ1,000 stock solutions in distilled water and diluted into Krebs solution.…”

Section: Methodsmentioning

confidence: 99%

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Endothelial coordination of cerebral vasomotion via myoendothelial gap junctions containing connexins 37 and 40

Haddock

Grayson²,

Brackenbury³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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114

116

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Control of cerebral vasculature differs from that of systemic vessels outside the blood-brain barrier. The hypothesis that the endothelium modulates vasomotion via direct myoendothelial coupling was investigated in a small vessel of the cerebral circulation. In the primary branch of the rat basilar artery, membrane potential, diameter, and calcium dynamics associated with vasomotion were examined using selective inhibitors of endothelial function in intact and endothelium-denuded arteries. Vessel anatomy, protein, and mRNA expression were studied using conventional electron microscopy high-resolution ultrastructural and confocal immunohistochemistry and quantitative PCR. Membrane potential oscillations were present in both endothelial cells and smooth muscle cells (SMCs), and these preceded rhythmical contractions during which adjacent SMC intracellular calcium concentration ([Ca 2ϩ ]i) waves were synchronized. Endothelium removal abolished vasomotion and desynchronized adjacent smooth muscle cell [Ca 2ϩ ]i waves. N G -nitro-L-arginine methyl ester (10 M) did not mimic this effect, and dibutyryl cGMP (300 M) failed to resynchronize [Ca 2ϩ ]i waves in endothelium-denuded arteries. Combined charybdotoxin and apamin abolished vasomotion and depolarized and constricted vessels, even in absence of endothelium. Separately, 37,43 Gap27 and 40 Gap27 abolished vasomotion. Extensive myoendothelial gap junctions (3 per endothelial cell) composed of connexins 37 and 40 connected the endothelial cell and SMC layers. Synchronized vasomotion in rat basilar artery is endothelium dependent, with [Ca 2ϩ ]i waves generated within SMCs being coordinated by electrical coupling via myoendothelial gap junctions.connexin; electron microscopy; endothelial function; potassium channel; membrane potential VASOMOTION is an intrinsic feature of many arteries and arterioles under normal and pathological conditions and may contribute to regulation of blood flow and pressure (1,14). Both spontaneous and agonist-induced vasomotion occur when oscillations in the concentration of intracellular calcium ([Ca 2ϩ ] i ) become synchronized among adjacent smooth muscle cells, giving rise to global oscillations in [Ca 2ϩ ] i across the vessel wall (13,15,26,27,33,41,(47)(48)(49).There is clear heterogeneity in the mechanisms that underlie vasomotion, and specifically whether the endothelium plays a mandatory or modulatory role. In the rat iris arteriole, rabbit ear, and superior mesenteric artery, vasomotion is reported to be endothelium independent (3, 18, 39), whereas in the rat mesenteric, rabbit femoral artery, and hamster aorta, vasomotion is suggested to be endothelium dependent, as shown by its abolition with endothelium denudation (12,21,34,38,40).Endothelium-dependent effects on vasomotion have been attributed to the vasodilatory factors nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). In some studies, endothelial cells play an essential role in synchronizing the activity of smooth muscle cells through the rel...

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Functional Role of Connexins and Pannexins in the Interaction Between Vascular and Nervous System

Gaete

Lillo

Figueroa

2014

Journal Cellular Physiology

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The microvascular network of the microcirculation works in tight communication with surrounding tissues to control blood supply and exchange of solutes. In cerebral circulation, microvascular endothelial cells constitute a selective permeability barrier that controls the environment of parenchymal brain tissue, which is known as the blood-brain barrier (BBB). Connexin- and pannexin-formed channels (gap junctions and hemichannels) play a central role in the coordination of endothelial and smooth muscle cell function and connexin-mediated signaling in endothelial cells is essential in the regulation of BBB permeability. Likewise, gap junction communication between astrocyte end-feet also contributes to maintain the BBB integrity, but the participation of hemichannels in this process cannot be discarded. Sympathetic and sensory perivascular nerves are also involved in the control and coordination of vascular function through the release of vasoconstrictor or vasodilator signals and by the regulation of gap junction communication in the vessel wall. Conversely, ATP release through pannexin-1-formed channels mediates the α1-adrenergic signaling. Furthermore, here we show that capsaicin-induced CGRP release from mesenteric perivascular sensory nerves induces pannexin-1-formed channel opening, which in turn leads to reduction of pannexin-1 and endothelial nitric oxide synthase (eNOS) expression along the time. Interestingly, blockade of CGRP receptors with CGRP8-37 increased eNOS expression by ∼5-fold, suggesting that capsaicin-sensitive sensory nerves are involved in the control of key signaling proteins for vascular function. In this review, we discuss the importance of connexin-based channels in the control of BBB integrity and the functional interaction of vascular connexins and pannexins with the peripheral nervous system.

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Decreased endothelial size and connexin expression in rat caudal arteries during hypertension

Abstract: The development of hypertension in the SHR is accompanied by significant decreases in endothelial cell size and expression of Cx40, which may contribute to the endothelial dysfunction present in hypertension.

Cited by 50 publications

References 26 publications

Downregulation of connexin40 is associated with coronary endothelial cell dysfunction in streptozotocin-induced diabetic mice

Downregulation of connexin40 is associated with coronary endothelial cell dysfunction in streptozotocin-induced diabetic mice

Endothelial coordination of cerebral vasomotion via myoendothelial gap junctions containing connexins 37 and 40

Functional Role of Connexins and Pannexins in the Interaction Between Vascular and Nervous System

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