Endogenous angiotensin II has fewer effects but neuronal nitric oxide synthase has excitatory effects on renal sympathetic nerve activity in salt-sensitive hypertension-induced heart failure

Kemuriyama, Takehito; Tandai-Hiruma, Megumi; Kato, Kazuo; Ohta, Hiroyuki; Maruyama, Satoshi; Sato, Yuzo; Nishida, Yasuhiro

doi:10.1007/s12576-009-0034-x

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…Although the immunofluorescence showed that the contents of Col-I and Col-III were significantly reduced, Sirius Red staining showed that myocardial fibrosis in diabetic rats which trained for 8 weeks was not fully inhibited, possibly due to the relatively short duration of single-bout exercise. Exercise can reduce the degree of myocardial fibrosis, which may be related to such factors as reduced oxidative stress in diabetic myocardium, attenuated activity of renin angiotensin and inhibited advanced glycosylation end products (AGEs) [29,30]. Further, moderate exercise was reported to increase mitochondrial adaptations which potentially suppress fibrosis-related oxidative stress in T2DM; these thus preserve cardiac function from the perspective of energy metabolism [31,32].…”

Section: Discussionmentioning

confidence: 99%

Long-term moderate intensity exercise alleviates myocardial fibrosis in type 2 diabetic rats via inhibitions of oxidative stress and TGF-β1/Smad pathway

Wang

Yuan

2019

J Physiol Sci

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Exercise has an effect on the reduction of myocardial fibrosis in diabetic rats as previously reported, in which oxidative stress and the TGF-β1/Smad signaling pathway may play key roles. There is little direct experimental evidence that exercise alleviates myocardial fibrosis in type 2 diabetes mellitus (T2DM). Here we established a type 2 diabetic model by using streptozotocin and a high-fat diet. Rats were divided into groups of normal control (NC), T2DM and T2DM plus exercise (T2DME). The T2DME group received further treadmill training at moderate intensity for 8 weeks. Histological and biochemical methods were used to detect the benefits of exercise to T2DM. Results showed that the weight of rats in the T2DM group dropped dramatically, along with significant increases in blood glucose, myocardial fibrosis and oxidative stress, associated with upregulated expression of factors of myocardial fibrosis, except Smad7. Exercise largely reversed T2DMinduced alterations in factors of myocardial fibrosis, including suppressing expression of MMP-2, CTGF, TGF-β1, p-Smad2 and p-Smad3, and increased expression of TIMP-1 and Smad7. Therefore, exercise might be considered an alternative therapeutic remedy for diabetic cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

Long-term moderate intensity exercise alleviates myocardial fibrosis in type 2 diabetic rats via inhibitions of oxidative stress and TGF-β1/Smad pathway

Wang

Yuan

2019

J Physiol Sci

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“…RGS4 protein was determined by Western blotting. Mice were treated with L-NAME (0.5 g/l; Sigma-Aldrich) or with SMTC (10 mg/kg/d; Sigma-Aldrich) in the drinking water (63)(64)(65). Littermates inheriting only responder or driver transgene were used as controls and were treated similarly.…”

Section: Hypertrophic Marker Gene Expressionmentioning

confidence: 99%

NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth

Jaba¹,

Zhuang²,

Li³

et al. 2013

J. Clin. Invest.

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Myocardial hypertrophy is an adaptation to increased hemodynamic demands. An increase in heart tissue must be matched by a corresponding expansion of the coronary vasculature to maintain and adequate supply of oxygen and nutrients for the heart. The physiological mechanisms that underlie the coordination of angiogenesis and cardiomyocyte growth are unknown. We report that induction of myocardial angiogenesis promotes cardiomyocyte growth and cardiac hypertrophy through a novel NO-dependent mechanism. We used transgenic, conditional overexpression of placental growth factor (PlGF) in murine cardiac tissues to stimulate myocardial angiogenesis and increase endothelial-derived NO release. NO production, in turn, induced myocardial hypertrophy by promoting proteasomal degradation of regulator of G protein signaling type 4 (RGS4), thus relieving the repression of the Gβγ/PI3Kγ/AKT/mTORC1 pathway that stimulates cardiomyocyte growth. This hypertrophic response was prevented by concomitant transgenic expression of RGS4 in cardiomyocytes. NOS inhibitor L-NAME also significantly attenuated RGS4 degradation, and reduced activation of AKT/mTORC1 signaling and induction of myocardial hypertrophy in PlGF transgenic mice, while conditional cardiac-specific PlGF expression in eNOS knockout mice did not induce myocardial hypertrophy. These findings describe a novel NO/RGS4/Gβγ/PI3Kγ/AKT mechanism that couples cardiac vessel growth with myocyte growth and heart size. IntroductionRecent studies have increased appreciation for the relationship between cardiomyocyte growth and angiogenesis and its contribution to molecular regulation of the myocardial hypertrophic response. Myocardial hypertrophy, secondary to increased hemodynamic demands, requires commensurate growth of the coronary vasculature to provide adequate oxygen and nutrients to the increasing cardiac mass; lack of coordination between the myocyte-driven hypertrophic response and the production of angiogenic growth factors hallmarks the transition to heart failure (1). Although vascular endothelium controls a plethora of biological events contributing to cardiovascular homeostasis, including regulation of vascular tone, thrombosis, and myocardial stiffness, little is known about the effect of endothelial signaling on cardiomyocyte growth, regulation of myocardial hypertrophy, and heart size. Our previous observation that a NOS inhibitor, N G -nitro-l-arginine methyl ester (L-NAME), partially prevented angiogenesis-driven myocardial hypertrophy (2) suggests that endothelium-dependent NO production might be responsible for the hypertrophic effect on cardiomyocytes and the increase in heart size.Because there are no known mechanisms that link NO to stimulation of cardiomyocyte hypertrophy, we designed the present study to fill this gap. In cardiomyocytes, G protein-mediated hypertrophic signaling is negatively modulated by regulators of G protein signaling (RGS proteins). Among more than 20 RGS proteins, RGS subtype 4, a GTPase-activating protein for heterotrimeric Gq and ...

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“…The two most popular methods to generate whole-body gene deletions and conditional knockouts are Cre/loxP and Flippase/FRT-mediated recombination methods [ 16 ]. Hypertension-induced CHF model does not require additional interventions but the modeling time is too long [ 17 , 18 ].Drug induction mainly includes doxorubicin and isoproterenol, which have the advantages of easy operation, short modeling time and low infection rate [ 19 , 20 ]. For doxorubicin, its mortality rate is higher and it is not in line with the etiology of most HF patients while for isoproterenol, it is affected by animal batch, drug batch, route of administration, etc.…”

Section: Introductionmentioning

confidence: 99%

Effect of injection of different doses of isoproterenol on the hearts of mice

Pan

Gao

et al. 2022

BMC Cardiovasc Disord

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Background Heart failure (HF) is one of the diseases that seriously threaten human health today and its mechanisms are very complex. Our study aims to confirm the optimal dose ISO-induced chronic heart failure mice model for better study of HF-related mechanisms and treatments in the future. Methods C57BL/6 mice were used to establish mice model of chronic heart failure. We injected isoproterenol subcutaneously in a dose gradient of 250 mg/kg, 200 mg/kg, 150 mg/kg, 100 mg/kg and 50 mg/kg. Echocardiography and ELISA were performed to figure out the occurrence of HF. We also supplemented the echocardiographic changes in mice over 30 days. Results Except group S and group E, echocardiographic abnormalities were found in other groups, suggesting a decrease in cardiac function. Except group S, myofibrolysis were found in the hearts of mice in other groups. Brain natriuretic peptide was significantly increased in groups B and D, and C-reactive protein was significantly increased in each group. Conclusion Our research finally found that the HFrEF mice model created by injection at a dose of 100 mg/kg for 7 days was the most suitable and a relatively stable chronic heart failure model could be obtained by placing it for 21 days.

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Endogenous angiotensin II has fewer effects but neuronal nitric oxide synthase has excitatory effects on renal sympathetic nerve activity in salt-sensitive hypertension-induced heart failure

Cited by 4 publications

References 33 publications

Long-term moderate intensity exercise alleviates myocardial fibrosis in type 2 diabetic rats via inhibitions of oxidative stress and TGF-β1/Smad pathway

Long-term moderate intensity exercise alleviates myocardial fibrosis in type 2 diabetic rats via inhibitions of oxidative stress and TGF-β1/Smad pathway

NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth

Effect of injection of different doses of isoproterenol on the hearts of mice

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