Disruption of endothelial caveolae is associated with impairment of both NO- as well as EDHF in acetylcholine-induced relaxation depending on their relative contribution in different vascular beds

Xu, Ying; Henning, Robert H.; Want, J.J.L. van der; Buiten, van Azuwerus; Gilst, van Wiekert; Buikema, Hendrik

doi:10.1016/j.lfs.2007.01.041

Cited by 27 publications

(25 citation statements)

References 48 publications

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“…On the other hand, in renal arteries and mesenteric arteries from normotensive rats treated with 1 mM CD, relaxation by SNP was not impaired (Xu et al, 2007). In the same way, in rabbit aorta treated with 2% 2-hydroxypropyl-␤-cyclodextrin relaxation by SNP was not impaired either (Darblade et al, 2001).…”

Section: Discussionmentioning

confidence: 88%

Caveolae Dysfunction Contributes to Impaired Relaxation Induced by Nitric Oxide Donor in Aorta from Renal Hypertensive Rats

Rodrigues

Restini

Lunardi

et al. 2007

J Pharmacol Exp Ther

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Relaxation induced by nitric oxide (NO) donors is impaired in renal hypertensive two kidney-one clip (2K-1C) rat aortas. It has been proposed that caveolae are important in signal transduction and Ca 2ϩ homeostasis. Therefore, in the present study we investigate the integrity of caveolae in vascular smooth muscle cells (VSMCs), as well as their influence on the effects produced by NO released from both the new NO donor [Ru(NH.NHq) (terpy)NO ϩ ] 3ϩ (TERPY) and sodium nitroprusside (SNP) on 2K-1C rat aorta. The potency of both TERPY and SNP was lower in the 2K-1C aorta that in the normotensive aorta [two kidney (2K)], whereas the maximal relaxant effect (ME) was similar in both 2K-1C and 2K aortas. In the 2K aorta, methyl-␤-cyclodextrin (CD) reduced both the potency of TERPY and SNP, and their ME compared with the control, but it had no effect on the potency and ME of these NO donors in 2K-1C aortas. The decrease in cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] c ) induced by TERPY was larger in 2K than in 2K-1C cells, and this effect was inhibited by CD in 2K cells only. Aortic VSMCs from 2K rats presented a larger number of caveolae than those from 2K-1C rats. Treatment with CD reduced the number of caveolae in both 2K and 2K-1C aortic VSMCs. Our results support the idea that caveolae play a critical role in the relaxant effect and in the decrease in [Ca 2ϩ

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Section: Discussionmentioning

confidence: 88%

Caveolae Dysfunction Contributes to Impaired Relaxation Induced by Nitric Oxide Donor in Aorta from Renal Hypertensive Rats

Rodrigues

Restini

Lunardi

et al. 2007

J Pharmacol Exp Ther

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“…Acetylcholine-induced relaxation has been shown to be decreased after membrane cholesterol depletion in different rat arteries [38,39], but either increased or not modified in systemic arteries isolated from…”

Section: Discussionmentioning

confidence: 99%

Role of Gi/o-Src kinase-PI3K/Akt pathway and caveolin-1 in β2-adrenoceptor coupling to endothelial NO synthase in mouse pulmonary artery

Banquet

Delannoy

Agouni

et al. 2011

Cellular Signalling

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“…In addition to that, the area under each individual curve (AUC; in arbitrary units) was determined for ACh-induced relaxation (SigmaPlot version 10.0, Systat Software, San Jose, CA). The AUC was used to present total endothelium-dependent relaxation and for the subsequent analysis of differences in ACh-mediated relaxation with and without inhibitors present to estimate the contribution of the different EDRFs, i.e., PGs for the part sensitive to cycloxygenase inhibition with indomethacin, NO for the part sensitive to NOS inhibition with L-NMMA, and EDHF by means of exclusion of PG and NO (34). Data are presented as means Ϯ SE, and n refers to the number of animals in each group.…”

Section: Animalsmentioning

confidence: 99%

“…22). CAV-1, a structural protein within the caveolus, has been identified as a key regulator of eNOS activity (34). In a recent study (3), it was demonstrated that the scaffolding domain of CAV-1 acts as an endogenous negative regulator of eNOS function, thereby limiting basal NO release.…”

Section: H714 Vascular Effects Of Gdf15mentioning

confidence: 99%

Growth differentiation factor 15 impairs aortic contractile and relaxing function through altered caveolar signaling of the endothelium

Mazagova

Buikema

Landheer

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Mazagova M, Buikema H, Landheer SW, Vavrinec P, van Buiten A, Henning RH, Deelman LE. Growth differentiation factor 15 impairs aortic contractile and relaxing function through altered caveolar signaling of the endothelium. Am J Physiol Heart Circ Physiol 304: H709 -H718, 2013. First published December 21, 2012 doi:10.1152/ajpheart.00543.2012.-Growth differentiation factor 15 (GDF15) is an independent predictor of cardiovascular disease, and increased GDF15 levels have been associated with endothelial dysfunction in selected patients. We therefore investigated whether GDF15 modulates endothelial function in aortas of wild-type (WT) and GDF15 knockout (KO) mice. Vascular contractions to phenylephrine and relaxation to ACh were assessed in aortas obtained from healthy WT and GDF15 KO mice. The effects of GDF15 pretreatment and the involvement of ROS or caveolae were determined. Phenylephrine-induced contractions and ACh-mediated relaxations were similar in WT and GDF15 KO mice. Pretreatment with GDF15 inhibited contraction and relaxation in both groups. Inhibition of contraction by GDF15 was absent in denuded vessels or after blockade of nitric oxide (NO) synthase. Relaxation in WT mice was mediated mainly through NO and an unidentified endothelium-derived hyperpolarizin factor (EDHF), whereas GDF15 KO mice mainly used prostaglandins and EDHF. Pretreatment with GDF15 impaired relaxation in WT mice by decreasing NO; in GDF15 KO mice, this was mediated by decreased action of prostaglandins. Disruption of caveolae resulted in a similar inhibition of vascular responses as GDF15. ROS inhibition did not affect vascular function. In cultured endothelial cells, GDF15 pretreatment caused a dissociation between caveolin-1 and endothelial NO synthase. In conclusion, GDF15 impairs aortic contractile and relaxing function through an endotheliumdependent mechanism involving altered caveolar endothelial NO synthase signaling. growth differentiation factor 15; aorta; endothelium; mice; caveolae; caveolin-1 GROWTH DIFFERENTIATION FACTOR 15 (GDF15), also called macrophage inhibitory cytokine (MIC)-1, is a distant member of the transforming growth factor (TGF)-␤ family and the result of posttranslational modification of the product of an early response gene (4). Upregulation of GDF15 has been demonstrated after chemical and hyperoxic injury of the lung, by surgical, chemical, and heat-induced injury of the liver (19), and after ischemia-reperfusion injury of the heart (15), indicating that GDF15 is a general mediator of the organ injury response. Furthermore, GDF15 is emerging as an independent predictor of cardiovascular disease (CVD) in the elderly and a predictor of prognosis in patients with established CVD (17,20,21). An association between GDF15 levels and endothelial dysfunction was found in an elderly population (21). Hence, endothelial dysfunction is considered the first step in the chain of events leading to atherosclerosis and CVD. It comprises an imbalanced production of vasodilating and vasoconstricting substances by th...

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Disruption of endothelial caveolae is associated with impairment of both NO- as well as EDHF in acetylcholine-induced relaxation depending on their relative contribution in different vascular beds

Cited by 27 publications

References 48 publications

Caveolae Dysfunction Contributes to Impaired Relaxation Induced by Nitric Oxide Donor in Aorta from Renal Hypertensive Rats

Caveolae Dysfunction Contributes to Impaired Relaxation Induced by Nitric Oxide Donor in Aorta from Renal Hypertensive Rats

Role of Gi/o-Src kinase-PI3K/Akt pathway and caveolin-1 in β2-adrenoceptor coupling to endothelial NO synthase in mouse pulmonary artery

Growth differentiation factor 15 impairs aortic contractile and relaxing function through altered caveolar signaling of the endothelium

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