Regression of ventricular and vascular hypertrophy

Raasch, Walter; Bartels, Torsten; Schwartz, Christopher; Haüser, Winfried; Rütten, Hartmut; Dominiak, Peter

doi:10.1097/00004872-200212000-00030

Cited by 24 publications

(2 citation statements)

References 28 publications

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“…This observation indicates that not only endogenously infused AII, but also endogenously produced AII is able to activate PARP in the vasculature. The dose of enalapril used in the current study has been shown to provide a full blockade of angiotensin-converting enzyme (ACE) and has been demonstrated to normalize blood pressure and cardiovascular function (28)(29)(30). The question may arise as to whether PARP activation in SHR animals is related to AII directly activating oxidative and nitrosative processes in the endothelial cells, or alternatively, to the physical phenomenon of hypertension, which could, in theory, enhance endothelial oxidant and free radical production via increased shear stress (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II-Mediated Endothelial Dysfunction: Role of Poly(ADP-ribose) Polymerase Activation

Szabó

Pacher

Zsengellér

et al. 2004

Mol Med

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Angiotensin II (AII) contributes to the pathogenesis of many cardiovascular disorders. Oxidant-mediated activation of poly(adenosine diphosphate-ribose) polymerase (PARP) plays a role in the development of endothelial dysfunction and the pathogenesis of various cardiovascular diseases. We have investigated whether activation of the nuclear enzyme PARP contributes to the development of AII-induced endothelial dysfunction. AII in cultured endothelial cells induced DNA single-strand breakage and dose-dependently activated PARP, which was inhibited by the AII subtype 1 receptor antagonist, losartan; the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin; and the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester. Infusion of sub-pressor doses of AII to rats for 7 to 14 d induced the development of endothelial dysfunction ex vivo. The PARP inhibitors PJ34 or INO-1001 prevented the development of the endothelial dysfunction and restored normal endothelial function. Similarly, PARP-deficient mice infused with AII for 7 d were found resistant to the AII-induced development of endothelial dysfunction, as opposed to the wild-type controls. In spontaneously hypertensive rats there was marked PARP activation in the aorta, heart, and kidney. The endothelial dysfunction, the cardiovascular alterations and the activation of PARP were prevented by the angiotensin-converting enzyme inhibitor enalapril. We conclude that AII, via AII receptor subtype 1 activation and reactive oxygen and nitrogen species generation, triggers DNA breakage, which activates PARP in the vascular endothelium, leading to the development of endothelial dysfunction in hypertension.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II-Mediated Endothelial Dysfunction: Role of Poly(ADP-ribose) Polymerase Activation

Szabó

Pacher

Zsengellér

et al. 2004

Mol Med

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“…The diet was abundantly offered, supplementary to chow, whereas controls received chow only (Miesel et al 2010). At regular intervals, blood pressure and heart rate were determined by plethysmography (Raasch et al 2002) and blood samples were withdrawn from a tail nick to measure blood glucose, plasma aldosterone and S1P levels. For S1P-induced aldosterone release, 200 µg/kg S1P was intravenously injected as described earlier in chow-vs CD-fed SHRs.…”

Section: S1p Effects On Plasma Aldosterone Of Diet-induced Obese Pitmentioning

confidence: 99%

Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism

Werth

Müller-Fielitz

Raasch

2017

Journal of Endocrinology

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Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. release of S1P (100-300 µg/kg) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely.

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Stellenwert der ACE‐Hemmer in der Hochdrucktherapie: Seit langem etabliert!

Dominiak

2003

Pharmazie in unserer Zeit

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Regression of ventricular and vascular hypertrophy

Cited by 24 publications

References 28 publications

Angiotensin II-Mediated Endothelial Dysfunction: Role of Poly(ADP-ribose) Polymerase Activation

Angiotensin II-Mediated Endothelial Dysfunction: Role of Poly(ADP-ribose) Polymerase Activation

Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism

Stellenwert der ACE‐Hemmer in der Hochdrucktherapie: Seit langem etabliert!

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