Ablation of angiotensin (1-7) receptor Mas in C57Bl/6 mice causes endothelial dysfunction

Rabelo, Luíza Antas; Xu, Ping; Todiras, Mihail; Sampaio, Walkyria Oliveira; Buttgereit, Jens; Bäder, Michael; Santos, Robson A.S.; Alenina, Natalia

doi:10.1016/j.jash.2008.05.003

Cited by 62 publications

(43 citation statements)

References 25 publications

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“…In addition the Mas knockout, mice are also reported to have changes in hemostasis (Fraga-Silva et al, 2008) and penile fibrosis (da Costa Goncalves et al, 2007). A common mechanism behind the Mas knockout mice, exhibiting altered heart rate and blood pressure, increased vascular resistance, and decrease blood flow, is thought to be endothelial dysfunction due to imbalances in nitric oxide (NO) and reactive oxygen species (Castro et al, 2005;da Costa Goncalves et al, 2007;Peiro et al, 2007;Rabelo et al, 2008;Xu et al, 2008;Raku san et al, 2010;Botelho-Santos et al, 2012).…”

Section: F Mas Gene-knockout In Micementioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

et al. 2015

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Section: F Mas Gene-knockout In Micementioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

et al. 2015

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“…This interaction improves endothelial function and reduces blood pressure by decreasing ROS and increasing NO levels, as we recently showed using Mas-deficient mice (117,118). Ang-(1-7) effects are mediated through stimulation of Aktphosphorylation and eNOS activity (116,119).…”

Section: Figurementioning

confidence: 75%

Tissue Renin-Angiotensin-Aldosterone Systems: Targets for Pharmacological Therapy

Bäder

2010

Annu. Rev. Pharmacol. Toxicol.

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287

235

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The renin-angiotensin-aldosterone system is one of the most important systems in cardiovascular control and in the pathogenesis of cardiovascular diseases. Therefore, it is already a very successful drug target for the therapy of these diseases. However, angiotensins are generated not only in the plasma but also locally in tissues from precursors and substrates either locally expressed or imported from the circulation. In most areas of the brain, only locally generated angiotensins can exert effects on their receptors owing to the blood-brain barrier. Other tissue renin-angiotensin-aldosterone systems are found in cardiovascular organs such as kidney, heart, and vessels and play important roles in the function of these organs and in the deleterious actions of hypertension and diabetes on these tissues. Novel components with mostly opposite actions to the classical renin-angiotensin-aldosterone systems have been described and need functional characterization to evaluate their suitability as novel drug targets.

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“…35 Indeed, we have shown recently that genetic deletion of Mas in FVB/N mice produced a significant increase in blood pressure associated with endothelium dysfunction. 36 An increase of vascular resistance in many organs 37 and a marked endothelium dysfunction 38 was also observed in Mas Ϫ/Ϫ C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 94%

Vascular Relaxation, Antihypertensive Effect, and Cardioprotection of a Novel Peptide Agonist of the Mas Receptor

Savergnini

Beiman²,

Lautner³

et al. 2010

Hypertension

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105

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Abstract-Mas stimulation with angiotensin (Ang)-(1-7) produces cardioprotective effects and vasorelaxation. Using a computational discovery platform for predicting novel naturally occurring peptides that may activate G protein-coupled receptors, we discovered a novel Mas agonist peptide, CGEN-856S. An endothelium-and NO-dependent vasodilating effect was observed for CGEN-856S in thoracic aorta rings of rats (maximal value for the relaxant effect: 39.99Ϯ5.034%), which was similar to that produced by Ang-(1-7) (10 Ϫ10 to 10 Ϫ6 mol/L). In addition, the vasodilator activity of this peptide depended on a functional Mas receptor, because it was abolished in aorta rings of Mas-knockout mice. CGEN-856S appears to bind the Mas receptor at the same binding domain as Ang- (1-7), as suggested by the blocking of its vasorelaxant effect with the Ang-(1-7) analogue D-Ala 7 -Ang-(1-7), and by its competitive inhibition of Ang-(1-7) binding to Mas-transfected cells. The effect of CGEN-856S on reperfusion arrhythmias and cardiac function was studied on ischemia reperfusion of isolated rat hearts. We found that picomolar concentration of CGEN-856S (0.04 nmol/L) had an antiarrhythmogenic effect, as demonstrated by a reduction in the incidence and duration of reperfusion arrhythmias. Furthermore, acute infusion of CGEN-856S produced a shallow dose-dependent decrease in mean arterial pressure of conscious spontaneously hypertensive rats. The maximum change during infusion was observed at the highest dose. Strikingly, blood pressure continued to drop in the postinfusion period. The results presented here indicate that the novel Mas agonist, CGEN-856S, might have a therapeutic value, because it induces vasorelaxing, antihypertensive, and cardioprotective effects. (Hypertension. 2010;56:112-120.)

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Ablation of angiotensin (1-7) receptor Mas in C57Bl/6 mice causes endothelial dysfunction

Cited by 62 publications

References 25 publications

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

Tissue Renin-Angiotensin-Aldosterone Systems: Targets for Pharmacological Therapy

Vascular Relaxation, Antihypertensive Effect, and Cardioprotection of a Novel Peptide Agonist of the Mas Receptor

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