Chronic infusion of angiotensin-(1–7) reduces heart angiotensin II levels in rats

Mendes, Ana Cristina; Ferreira, Anderson J.; Pinheiro, Sérgio Veloso Brant; Santos, Robson A.S.

doi:10.1016/j.regpep.2004.07.023

Cited by 51 publications

(41 citation statements)

References 39 publications

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“…These effects were completely blocked by the selective Ang-(1-7) receptor Mas antagonist A-779, suggesting that these Ang-(1-7) actions in the heart are mediated by its specific receptor. One possible mechanism that may contribute to the beneficial effects of Ang-(1-7) in the heart is the modulation of cardiac Ang II levels, as described recently by Mendes et al 29 The present results indicate that the Ang-(1-7) receptor Mas mediates the effects of Ang-(1-7) on the cardiac function.…”

Section: Discussionsupporting

confidence: 82%

Impairment of In Vitro and In Vivo Heart Function in Angiotensin-(1-7) Receptor Mas Knockout Mice

Santos¹,

Castro²,

Gava³

et al. 2006

Hypertension

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215

172

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Abstract-In this study we investigated the effects of the genetic deletion of the angiotensin (Ang)-(1-7) receptor Mas on heart function. Localization of Mas in the mouse heart was evaluated by binding of rhodamine-labeled Ang-(1-7). Cardiac function was examined using isolated heart preparations. Echocardiography was used to confirm the results obtained with isolated heart studies. To elucidate the possible mechanisms involved in the cardiac phenotype observed in Mas Ϫ/Ϫ mice, whole-cell calcium currents in cardiomyocytes and the expression of collagen types I, III, and VI and fibronectin were analyzed. Ang-(1-7) binding showed that Mas is localized in cardiomyocytes of the mouse heart. Isolated heart techniques revealed that Mas-deficient mice present a lower systolic tension (average: 1.4Ϯ0.09 versus 2.1Ϯ0.03 g in Mas ϩ/ϩ mice), ϮdT/dt, and heart rate. A significantly higher coronary vessel resistance was also observed in Mas-deficient mice. Echocardiography revealed that hearts of Mas-deficient mice showed a significantly decreased fractional shortening, posterior wall thickness in systole and left ventricle end-diastolic dimension, and a higher left ventricle end-systolic dimension. A markedly lower global ventricular function, as defined by a higher myocardial performance index, was observed. A higher delayed time to the peak of calcium current was also observed. The changes in cardiac function could be partially explained by a marked change in collagen expression to a profibrotic profile in Mas-deficient mice. These results indicate that Ang-(1-7)-Mas axis plays a key role in the maintenance of the structure and function of the heart. (Hypertension. 2006;47:996-1002.)

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Section: Discussionsupporting

confidence: 82%

Impairment of In Vitro and In Vivo Heart Function in Angiotensin-(1-7) Receptor Mas Knockout Mice

Santos¹,

Castro²,

Gava³

et al. 2006

Hypertension

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215

172

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“…SD rats submitted to chronic subcutaneous infusion of Ang-(1-7) presented a decrease in Ang II accompanied by an increase in ACE2 mRNA expression in the LV. 30 Ang II possesses an inhibitory effect on ACE2 mRNA expression in astrocytes and cardiomyocytes cultures, 31 suggesting that a tissue decrease in Ang II could contribute to increased ACE2. In addition, TG rats presented a reduction in angiotensinogen mRNA expression in the LV.…”

Section: Discussionmentioning

confidence: 99%

Lifetime Overproduction of Circulating Angiotensin-(1-7) Attenuates Deoxycorticosterone Acetate-Salt Hypertension-Induced Cardiac Dysfunction and Remodeling

Santiago

Guimaraes²,

Sirvente³

et al. 2010

Hypertension

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Abstract-We evaluated the development of arterial hypertension, cardiac function, and collagen deposition, as well as the level of components of the renin-angiotensin system in the heart of transgenic rats that overexpress an angiotensin (Ang)-(1-7)-producing fusion protein, TGR(A1-7)3292 (TG), which induces a lifetime increase in circulating levels of this peptide. After 30 days of the induction of the deoxycorticosterone acetate (DOCA)-salt hypertension model, DOCA-TG rats were hypertensive but presented a lower systolic arterial pressure in comparison with DOCA-SpragueDawley (SD) rats. In contrast to DOCA-SD rats that presented left ventricle (LV) hypertrophy and diastolic dysfunction, DOCA-TG rats did not develop cardiac hypertrophy or changes in ventricular function. In addition, DOCA-TG rats showed attenuation in mRNA expression for collagen type I and III compared with the increased levels of DOCA-SD rats. Ang II plasma and LV levels were reduced in SD and TG hypertensive rats in comparison with normotensive animals. DOCA-TG rats presented a reduction in plasma Ang-(1-7) levels; however, there was a great increase in Ang-(1-7) (Ϸ3-fold) accompanied by a decrease in mRNA expression of both angiotensin-converting enzyme and angiotensin-converting enzyme 2 in the LV. The mRNA expression of Mas and Ang II type 1 receptors in the LV was not significantly changed in DOCA-SD or DOCA-TG rats. This study showed that TG rats with increased circulating levels of Ang-(1-7) are protected against cardiac dysfunction and fibrosis and also present an attenuated increase in blood pressure after DOCA-salt hypertension. In addition, DOCA-TG rats showed an important local increase in Ang-(1-7) levels in the LV, which might have contributed to the attenuation of cardiac dysfunction and prefibrotic lesions. (Hypertension. 2010;55:889-896.)

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“…Third, ANG-(1-7) may increase collagen degradation by activating matrix metalloproteinases or by inhibiting tissue inhibitors of matrix metalloproteinases. Finally, ANG-(1-7) may inhibit the actions of various profibrotic factors such as norepinephrine, angiotensin II, TGF-␤, and/or endothelin-1, as ANG-(1-7) infusion has been reported to result in a reduction of cardiac ANG II levels (34). Future studies will be aimed at dissecting the possible mechanisms by which ANG-(1-7) reduces cardiac fibrosis in hypertension and to determine if this anti-fibrotic action also occurs in non-hypertensive fibrotic conditions.…”

Section: Discussionmentioning

confidence: 99%

Chronic angiotensin-(1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension

Grobe¹,

Mecca²,

Mao³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

190

162

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Grobe, Justin L., Adam P. Mecca, Haoyu Mao, and Michael J. Katovich. Chronic angiotensin-(1-7) prevents cardiac fibrosis in DOCA-salt model of hypertension. Am J Physiol Heart Circ Physiol 290: H2417-H2423, 2006. First published January 13, 2006 doi:10.1152/ajpheart.01170.2005.-Cardiac remodeling is a hallmark hypertension-induced pathophysiology. In the current study, the role of the angiotensin-(1-7) fragment in modulating cardiac remodeling was examined. Sprague-Dawley rats underwent uninephrectomy surgery and were implanted with a deoxycorticosterone acetate (DOCA) pellet. DOCA animals had their drinking water replaced with 0.9% saline solution. A subgroup of DOCA-salt animals was implanted with osmotic minipumps, which delivered angiotensin-(1-7) chronically (100 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ). Control animals underwent sham surgery and were maintained on normal drinking water. Blood pressure was measured weekly with the use of the tail-cuff method, and after 4 wk of treatment, blood pressure responses to graded doses of angiotensin II were determined by direct carotid artery cannulation. Ventricle size was measured, and cross sections of the heart ventricles were paraffin embedded and stained using Masson's Trichrome to measure interstitial and perivascular collagen deposition and myocyte diameter. DOCA-salt treatment caused significant increases in blood pressure, cardiac hypertrophy, and myocardial and perivascular fibrosis. Angiotensin-(1-7) infusion prevented the collagen deposition effects without any effect on blood pressure or cardiac hypertrophy. These results indicate that angiotensin-(1-7) selectively prevents cardiac fibrosis independent of blood pressure or cardiac hypertrophy in the DOCA-salt model of hypertension. deoxycorticosterone acetate; blood pressure; cardiac remodeling CARDIAC FIBROSIS is a major facet of hypertensive cardiac disease, and it interferes with the normal function and structure of the myocardium (8,61,62). Increased deposition of basement membrane collagen is a hallmark of the remodeling process, and it results in an increase in cardiac tissue stiffness. This remodeling predisposes the patient to an increased risk of adverse cardiac events, including myocardial ischemia, infarction, arrhythmias, and sudden cardiac death (61). Thus prevention and reversal of cardiac fibrosis are essential in the management of hypertensive heart disease.The renin-angiotensin-aldosterone system (RAAS) has been suggested to participate in the development of end-organ damage in hypertensive patients (2, 11). Support for this concept comes from clinical trials demonstrating that treatment of hypertensive patients with either angiotensin-converting enzyme (ACE) inhibitors (38, 53) or ANG II type 1 (AT 1 ) receptor blockers (41, 60) provides significant protection from, and even reversal of, end-organ damage. Animal studies have also demonstrated that ACE inhibitors and AT 1 receptor antagonists prevent cardiovascular injury (23,55,56) as well as protect against renal (3, 55, 57) and cerebral (55-57) inj...

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Chronic infusion of angiotensin-(1–7) reduces heart angiotensin II levels in rats

Cited by 51 publications

References 39 publications

Impairment of In Vitro and In Vivo Heart Function in Angiotensin-(1-7) Receptor Mas Knockout Mice

Impairment of In Vitro and In Vivo Heart Function in Angiotensin-(1-7) Receptor Mas Knockout Mice

Lifetime Overproduction of Circulating Angiotensin-(1-7) Attenuates Deoxycorticosterone Acetate-Salt Hypertension-Induced Cardiac Dysfunction and Remodeling

Chronic angiotensin-(1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension

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