Cardiac Morphofunctional Characteristics of Transgenic Rats With Overexpression of the Bradykinin B1 Receptor in the Endothelium

Levy, Rozeli Ferreira; Serra, Andrey Jorge; Antônio, Ednei Luiz; Santos, Leonardo dos; Bocalini, Danilo Sales; Pesquero, João Bosco; Bäder, Michael; Merino, Vanessa F.; Oliveira, Helenita Antônia de; Veiga, Eduardo Carvalho de Arruda; Silva, J. A.; Tucci, Paulo José Ferreira

doi:10.33549/physiolres.933596

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…Immediately after blood sample collection, the heart was quickly removed and placed in oxygenated Krebs-Henseleit nutrient solution. As detailed elsewhere [14,15], the papillary muscle of the left ventricle was carefully dissected and mounted vertically in a chamber containing nutrient solution oxygenated with 100% O 2 at 30 o C and pH adjusted to 7.40. The composition of the solution was (mmol/l): NaCl 132; KCl 4.69; CaCl 2 1.5; MgSO 4 1.16; KH 2 PO 4 1.18; C 6 H 12 O 6 5.50; HEPES 20.…”

Section: 'In Vitro' Cardiac Muscle Mechanicsmentioning

confidence: 99%

Physical exercise attenuates stress-induced hypertension in rats but not the impairments on the myocardial mechanics

Silva

Perilhão

Portes

et al. 2021

Journal of Hypertension

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Background: Acute and chronic stresses have become a health problem in the contemporary society, and prolonged exposure to stressful events are related to the pathogenesis of cardiovascular diseases. Physical exercise is a well-recognized effective nonpharmacological therapy for cardiovascular diseases and stress-induced injuries. Thus, this study evaluated the effect of exercise on the cardiac remodelling of chronically stressed rats.Methods and results: Wistar adult rats were used (n ¼ 10 each group) and chronic stress protocol consisted of restricting movement in individual rodent restrainers (60 min, 5 days/week, 12 weeks); and exercise consisted of swimming sessions in a pool (60 min, 5 days/week, 12 weeks). During protocol, blood pressure was measured in conscious rats, and at the end cardiac morphology/ function was assessed. Animals exposed to stress exhibited continuous rise in blood pressure from the sixth week, but exercise attenuated it. Similarly, restrained rats increased serum corticosterone compared with nonstressed rats, but exercise also prevented it. No changes were found in cardiac mass, but chronic stress not only impaired the steady state contractions of the cardiac muscle, but also reduced inotropic responses to stretching, increasing calcium and beta-adrenergic receptor stimulation. Despite this, exercise was unable to prevent these functional impairments induced by stress, and instead, the association of stress and physical exercise worsened myocardial compliance. Conclusion:Despite the known benefits to the cardiovascular system, our results indicate that aerobic swimming exercise for 12 weeks reduced blood pressure but did not impede the chronic stress-induced myocardial damages in rats.

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Section: 'In Vitro' Cardiac Muscle Mechanicsmentioning

confidence: 99%

Physical exercise attenuates stress-induced hypertension in rats but not the impairments on the myocardial mechanics

Silva

Perilhão

Portes

et al. 2021

Journal of Hypertension

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Role of Endothelial Kinin B1 Receptor on the Membrane Potential of Transgenic Rat Aorta

Batista

Sales²,

Merino³

et al. 2022

Physiol Res

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The kinin receptors are classically involved in inflammation, pain and sepsis. The effects of the kinin B1 receptor agonist des-Arg9-bradykinin (DBK) and lipopolysaccharide (LPS) were investigated by comparing the membrane potential responses of aortic rings from transgenic rats overexpressing the kinin B1 receptor (B1R) in the endothelium (TGR(Tie2B1)) and Sprague Dawley (SD) rats. No difference in the resting membrane potential in the aorta’s smooth muscle from the transgenic and SD rats was observed. The aorta rings from SD rats hyperpolarized only to LPS but not to DBK, whereas the aorta rings from TGR(Tie2B1) responded by the administration of both drugs. DBK and LPS responses were inhibited by the B1 receptor antagonist R715 and by iberiotoxin in both cases. Thapsigargin induced a hyperpolarization in the smooth muscle of SD rats that was not reversed by R715, but was reversed by iberiotoxin and this hyperpolarization was further augmented by DBK administration. These results show that the model of overexpression of vascular B1 receptors in the TGR(Tie2B1) rats represent a good model to study the role of functional B1 receptors in the absence of any pathological stimulus. The data also show that KCa channels are the final mediators of the hyperpolarizing responses to DBK and LPS. In addition, we suggest an interaction between the B1R and TLR4, since the hyperpolarization induced by LPS could be abolished in the presence of R715.

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Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil

Oumeiri

Dewachter

Borne

et al. 2023

Genes

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To explore the impact of omecamtiv mecarbil (OM) on the gene expression profile in adult male rats. Fourteen male Wistar rats were randomly assigned to a single OM (1.2 mg/kg/h; n = 6) or placebo (n = 8) 30-min infusion. Echocardiography was performed before and after OM infusion. Seven days after infusion, rats were euthanized, and left ventricular (LV) tissues were removed for real-time quantitative polymerase chain reaction (RTq-PCR) experiments. After OM infusion, pro-apoptotic Bax-to-Bcl2 ratio was decreased, with increased Bcl2 and similar Bax gene expression. The gene expression of molecules regulating oxidative stress, including glutathione disulfide reductase (Gsr) and superoxide dismutases (Sod1/Sod2), remained unchanged, whereas the expression of antioxidant glutathione peroxidase (Gpx) increased. While LV gene expression of key energy sensors, peroxisome proliferator activator (Ppar) α and γ, AMP-activated protein kinase (Ampk), and carnitine palmitoyltransferase 1 (Cpt1) remained unchanged after OM infusion, and the expression of pyruvate dehydrogenase kinase 4 (Pdk4) increased. The LV expression of the major myocardial glucose transporter Glut1 decreased, with no changes in Glut4 expression, whereas the LV expression of oxidized low-density lipoprotein receptor 1 (Olr1) and arachidonate 15-lipoxygenase (Alox15) increased, with no changes in fatty acid transporter Cd36. An increased LV expression of angiotensin II receptors AT1 and AT2 was observed, with no changes in angiotensin I-converting enzyme expression. The Kalikrein-bradykinin system was upregulated with increased LV expression of kallikrein-related peptidases Klk8, Klk1c2, and Klk1c12 and bradykinin receptors B1 and B2 (Bdkrb1 and Bdkrb2), whereas the LV expression of inducible nitric oxide synthase 2 (Nos2) increased. LV expression in major molecular determinants involved in calcium-dependent myocardial contraction remained unchanged, except for an increased LV expression of calcium/calmodulin-dependent protein kinase II delta (Cacna1c) in response to OM. A single intravenous infusion of OM, in adult healthy rats, resulted in significant changes in the LV expression of genes regulating apoptosis, oxidative stress, metabolism, and cardiac contractility.

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Cardiac Morphofunctional Characteristics of Transgenic Rats With Overexpression of the Bradykinin B1 Receptor in the Endothelium

Cited by 3 publications

References 24 publications

Physical exercise attenuates stress-induced hypertension in rats but not the impairments on the myocardial mechanics

Physical exercise attenuates stress-induced hypertension in rats but not the impairments on the myocardial mechanics

Role of Endothelial Kinin B1 Receptor on the Membrane Potential of Transgenic Rat Aorta

Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil

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