P8-03 Distinct effects of atenolol and carvedilol on aortic endothelial gap junctions in hypertensive rat

Lee, Ping-Ying; Su, Cheng‐Huang; Tsai, Cheng‐Ho; Yeh, Hung‐I

doi:10.1016/s0167-5273(04)80209-2

International Journal of Cardiology

2004

DOI: 10.1016/s0167-5273(04)80209-2

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P8-03 Distinct effects of atenolol and carvedilol on aortic endothelial gap junctions in hypertensive rat

Ping-Ying Lee¹,

Cheng‐Huang Su²,

Cheng‐Ho Tsai³

et al.

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2011

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“…Our previous study showed that downregulation of endothelial gap junctions is a common phenomenon in various disorders that induce and accelerate atherosclerosis (16), such as hypertension (23), hyperlipidemia (49), and diabetes (15) in cases where endothelial dysfunction exists. In addition, we (46) recently reported that in cultured endothelial cells, reduction of gap junctions per se leads to the development of endothelial dysfunction.…”

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Effects of carbenoxolone on flow-mediated vasodilatation in healthy adults

Lan

Hou

Yen

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Gap junctions play a key role in maintaining the functional integrity of the vascular wall. Using carbenoxolone (CBX) as a gap junction blocker, we aimed to assess the contribution of gap junctions in the vascular wall to flow-mediated vasodilatation (FMD) in healthy adults. Percentage FMD (%FMD) and circulating vasoactive molecules/activity, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), aldosterone, cortisol, plasma renin activity (PRA), and endothelin (ET-1) , were measured in 25 healthy volunteers (mean age: 30.1 Ϯ 5.4 yr; 14 males) before and after oral administration of CBX (100 mg). %FMD decreased after ingestion of CBX (9.71 Ϯ 3.1 vs. 3.40 Ϯ 2.0%; P Ͻ 0.0001). The levels of ANP, BNP, cortisol, and ET-1 remained stationary, while both PRA and aldosterone decreased (P Ͻ 0.005) after CBX ingestion. Blood pressure and heart rate were minimally changed by CBX. Inhibition of gap junctional communication by CBX impairs FMD in healthy persons, suggesting that physiologically, vascular gap junctions participate in the maintenance of FMD. CBX does not induce the release of vasoconstricting molecules or enhance vasoconstriction, suggesting that inhibition of gap junctional communication by CBX underlies the impairment of FMD. Therefore, administering CBX in FMD examination can be a way to follow the effect of gap junctions on endothelial function, but further work remains to verify the specificity of CBX effect. flow-mediated dilation; gap junctions; vasoactive molecules THE VASCULAR ENDOTHELIUM PLAYS a central role in the regulation of vasomotor tone, thrombogenecity, and inflammation (33). Endothelial dysfunction, an indicator of impairment of these regulatory mechanisms, is a systemic disorder and a key early event in the pathogenesis of atherosclerosis (29,44). In fact, endothelial dysfunction can be detected long before the appearance of structural atherosclerotic disease and is associated with increased cardiovascular risk (47). Accumulated data indicated that atherosclerotic cardiovascular disease also affects endothelial gap junctions, which are involved in maintaining functional integrity of the endothelium (21,22,48).Gap junctions are cell membrane protein channels made of connexins. Our previous study showed that downregulation of endothelial gap junctions is a common phenomenon in various disorders that induce and accelerate atherosclerosis (16), such as hypertension (23), hyperlipidemia (49), and diabetes (15) in cases where endothelial dysfunction exists. In addition, we (46) recently reported that in cultured endothelial cells, reduction of gap junctions per se leads to the development of endothelial dysfunction. However, all of this information comes from cell culture and animal experiments; thus, the contribution of gap junctions to the maintenance of endothelial function in humans remains unclear. To clarify the role of gap junctions, we hypothesized that gap junction blockade impairs flow-mediated vasodilatation (FMD), a clinically applicable examination for evaluat...

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Effects of carbenoxolone on flow-mediated vasodilatation in healthy adults

Lan

Hou

Yen

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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P8-03 Distinct effects of atenolol and carvedilol on aortic endothelial gap junctions in hypertensive rat

Cited by 1 publication

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Effects of carbenoxolone on flow-mediated vasodilatation in healthy adults

Effects of carbenoxolone on flow-mediated vasodilatation in healthy adults

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