Cross talk between kinin and angiotensin II receptors in mouse abdominal aorta

Rodrigues, Eliete S.; Martin, Renan Paulo; Felipe, Sandra A.; Bäder, Michael; Oliveira, Sérgio Ferreira de; Shimuta, Suma I.

doi:10.1515/bc.2009.081

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…Furthermore, other important genes are affected by genetic deletion of either kinin receptor. For instance, genetic disruption of B 1 R or B 2 R and both receptors decreased ACE and ANG II AT 1 R function and expression in mice abdominal aorta, indicating that kinin receptors regulate AT 1 receptors and ACE [76], [77]. Moreover, B 2 R knockout mice have increased ANG II AT 2 R mRNA and protein expression that contributes to elevation of NO as compensatory protective mechanism in thrombosis [78].…”

Section: Discussionmentioning

confidence: 99%

Kinin B1 Receptor Enhances the Oxidative Stress in a Rat Model of Insulin Resistance: Outcome in Hypertension, Allodynia and Metabolic Complications

et al. 2010

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BackgroundKinin B1 receptor (B1R) is induced by the oxidative stress in models of diabetes mellitus. This study aims at determining whether B1R activation could perpetuate the oxidative stress which leads to diabetic complications.Methods and FindingsYoung Sprague-Dawley rats were fed with 10% D-Glucose or tap water (controls) for 8–12 weeks. A selective B1R antagonist (SSR240612) was administered acutely (3–30 mg/kg) or daily for a period of 7 days (10 mg/kg) and the impact was measured on systolic blood pressure, allodynia, protein and/or mRNA B1R expression, aortic superoxide anion (O2 •−) production and expression of superoxide dismutase (MnSOD) and catalase. SSR240612 reduced dose-dependently (3–30 mg/kg) high blood pressure in 12-week glucose-fed rats, but had no effect in controls. Eight-week glucose-fed rats exhibited insulin resistance (HOMA index), hypertension, tactile and cold allodynia and significant increases of plasma levels of glucose and insulin. This was associated with higher aortic levels of O2 •−, NADPH oxidase activity, MnSOD and catalase expression. All these abnormalities including B1R overexpression (spinal cord, aorta, liver and gastrocnemius muscle) were normalized by the prolonged treatment with SSR240612. The production of O2 •− in the aorta of glucose-fed rats was also measured in the presence and absence of inhibitors (10–100 µM) of NADPH oxidase (apocynin), xanthine oxidase (allopurinol) or nitric oxide synthase (L-NAME) with and without Sar[D-Phe8]des-Arg9-BK (20 µM; B1R agonist). Data show that the greater aortic O2 •− production induced by the B1R agonist was blocked only by apocynin.ConclusionsActivation of kinin B1R increased O2 •− through the activation of NADPH oxidase in the vasculature. Prolonged blockade of B1R restored cardiovascular, sensory and metabolic abnormalities by reducing oxidative stress and B1R gene expression in this model.

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Section: Discussionmentioning

confidence: 99%

Kinin B1 Receptor Enhances the Oxidative Stress in a Rat Model of Insulin Resistance: Outcome in Hypertension, Allodynia and Metabolic Complications

et al. 2010

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“…Therefore several transgenic animals have been created, such as mice deficient in the kinin B 1 R [21,28], in the kinin B 2 R [5,9,10,12] and also in both kinin B 1 R and B 2 R [8], as well as mice overexpressing the B 1 R [17,19] or the B 2 R [34]. It has been shown that the lack of kinin receptors may affect the reactivity of the vascular smooth muscle preparations or cause changes in the expression level of some receptors of kallikrein kinin system (KKS) and renin angiotensin system (RAS) in the same tissue [26].…”

Section: Introductionmentioning

confidence: 99%

Evidence that kinin B2 receptor expression is upregulated by endothelial overexpression of B1 receptors

et al. 2013

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Bradykinin (BK) and des-Arg(9)-bradykinin (DBK) of kallikrein-kinin system exert its effects mediated by the B2 (B2R) and B1 (B1R) receptors, respectively. It was already shown that the deletion of kinin B1R or of B2R induces upregulation of the remaining receptor subtype. However studies on overexpression of B1R or B2R in transgenic animals have supported the importance of the overexpressed receptor but the expression of another receptor subtype has not been determined. Previous study described a marked vasodilatation and increased susceptibility to endotoxic shock which was associated with increased mortality in response to DBK in thoracic aorta from transgenic rat overexpressing the kinin B1R (TGR(Tie2B1)) exclusively in the endothelium. In another study, mice overexpressing B1R in multiple tissues were shown to present high susceptibility to inflammation and to lipopolysaccharide-induced endotoxic shock. Therefore the role of B2R was investigated in the thoracic aorta isolated from TGR(Tie2B1) rats overexpressing the B1R exclusively in the vascular endothelium. Our findings provided evidence for highly increased expression level of the B2R in the transgenic rats. It was reported that under endotoxic shock, these rats exhibited exaggerated hypotension, bradycardia and mortality. It can be suggested that the high mortality during the pathogenesis of endotoxic shock provoked in the transgenic TGR(Tie2B1) rats could be due to the enhanced expression of B2R associated with the overexpression of the B1R.

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“…Deletion of kinin receptors gene causes downregulation of ANG II receptors [31]. Therefore, a decrease in vascular AT1R expression may be involved in the anti-hypertrophic effects of the B1R antagonist.…”

Section: Discussionmentioning

confidence: 99%

An Interaction of Renin-Angiotensin and Kallikrein-Kinin Systems Contributes to Vascular Hypertrophy in Angiotensin II-Induced Hypertension: In Vivo and In Vitro Studies

et al. 2014

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The kallikrein-kinin and renin-angiotensin systems interact at multiple levels. In the present study, we tested the hypothesis that the B1 kinin receptor (B1R) contributes to vascular hypertrophy in angiotensin II (ANG II)–induced hypertension, through a mechanism involving reactive oxygen species (ROS) generation and extracellular signal-regulated kinase (ERK1/2) activation. Male Wistar rats were infused with vehicle (control rats), 400 ng/Kg/min ANG II (ANG II rats) or 400 ng/Kg/min ANG II plus B1 receptor antagonist, 350 ng/Kg/min des-Arg9-Leu8-bradykinin (ANGII+DAL rats), via osmotic mini-pumps (14 days) or received ANG II plus losartan (10 mg/Kg, 14 days, gavage - ANG II+LOS rats). After 14 days, ANG II rats exhibited increased systolic arterial pressure [(mmHg) 184±5.9 vs 115±2.3], aortic hypertrophy; increased ROS generation [2-hydroxyethidium/dihydroethidium (EOH/DHE): 21.8±2.7 vs 6.0±1.8] and ERK1/2 phosphorylation (% of control: 218.3±29.4 vs 100±0.25]. B1R expression was increased in aortas from ANG II and ANG II+DAL rats than in aortas from the ANG II+LOS and control groups. B1R antagonism reduced aorta hypertrophy, prevented ROS generation (EOH/DHE: 9.17±3.1) and ERK1/2 phosphorylation (137±20.7%) in ANG II rats. Cultured aortic vascular smooth muscle cells (VSMC) stimulated with low concentrations (0.1 nM) of ANG II plus B1R agonist exhibited increased ROS generation, ERK1/2 phosphorylation, proliferating-cell nuclear antigen expression and [H3]leucine incorporation. At this concentration, neither ANG II nor the B1R agonist produced any effects when tested individually. The ANG II/B1R agonist synergism was inhibited by losartan (AT1 blocker, 10 µM), B1R antagonist (10 µM) and Tiron (superoxide anion scavenger, 10 mM). These data suggest that B1R activation contributes to ANG II-induced aortic hypertrophy. This is associated with activation of redox-regulated ERK1/2 pathway that controls aortic smooth muscle cells growth. Our findings highlight an important cross-talk between the DABK and ANG II in the vascular system and contribute to a better understanding of the mechanisms involved in vascular remodeling in hypertension.

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Cross talk between kinin and angiotensin II receptors in mouse abdominal aorta

Cited by 7 publications

References 28 publications

Kinin B1 Receptor Enhances the Oxidative Stress in a Rat Model of Insulin Resistance: Outcome in Hypertension, Allodynia and Metabolic Complications

Kinin B1 Receptor Enhances the Oxidative Stress in a Rat Model of Insulin Resistance: Outcome in Hypertension, Allodynia and Metabolic Complications

Evidence that kinin B2 receptor expression is upregulated by endothelial overexpression of B1 receptors

An Interaction of Renin-Angiotensin and Kallikrein-Kinin Systems Contributes to Vascular Hypertrophy in Angiotensin II-Induced Hypertension: In Vivo and In Vitro Studies

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