Myocardial renin is neither necessary nor sufficient  to initiate or maintain ventricular hypertrophy

Katz, Stephen A.; Opsahl, John A.; Wernsing, Shane E.; Forbis, Lynn M.; Smith, Juline; Heller, Lois Jane

doi:10.1152/ajpregu.2000.278.3.r578

Cited by 11 publications

(16 citation statements)

References 45 publications

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“…There is also evidence that myocardial renin and angiotensinogen levels are decreased in this model (28). In line with these observations, plasma and LV levels of ANG II in both DOCA and DOCA-A7 rats were reduced.…”

Section: Discussionsupporting

confidence: 80%

Chronic infusion of angiotensin-(1-7) into the lateral ventricle of the brain attenuates hypertension in DOCA-salt rats

Guimaraes

Santiago

Xavier

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Angiotensin-(ANG)-(1-7) is known by its central and peripheral actions, which mainly oppose the deleterious effects induced by accumulation of ANG II during pathophysiological conditions. In the present study we evaluated whether a chronic increase in ANG-(1-7) levels in the brain would modify the progression of hypertension. After DOCA-salt hypertension was induced for seven days, Sprague-Dawley rats were subjected to 14 days of intracerebroventricular (ICV) infusion of ANG-(1-7) (200 ng/h, DOCA-A7) or 0.9% sterile saline. As expected, on the 21st day, DOCA rats presented increased mean arterial pressure (MAP) (≈40%), and impaired baroreflex control of heart rate (HR) and baroreflex renal sympathetic nerve activity (RSNA) in comparison with that in normotensive control rats (CTL). These changes were followed by an overactivity of the cardiac sympathetic tone and reduction of the cardiac parasympathetic tone, and exaggerated mRNA expression of collagen type I (≈9-fold) in the left ventricle. In contrast, DOCA rats treated with ANG-(1-7) ICV had an improvement of baroreflex control of HR, which was even higher than that in CTL, and a restoration of the baroreflex control of RSNA, the balance of cardiac autonomic tone, and normalized mRNA expression of collagen type I in the left ventricle. Furthermore, DOCA-A7 had MAP lowered significantly. These effects were not accompanied by significant circulating or cardiac changes in angiotensin levels. Taken together, our data show that chronic increase in ANG-(1-7) in the brain attenuates the development of DOCA-salt hypertension, highlighting the importance of this peptide in the brain for the treatment of cardiovascular diseases.

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Section: Discussionsupporting

confidence: 80%

Chronic infusion of angiotensin-(1-7) into the lateral ventricle of the brain attenuates hypertension in DOCA-salt rats

Guimaraes

Santiago

Xavier

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…The decrease in Ang II levels in the LV after DOCA-salt is in agreement with the observation of a decrease in myocardial renin and angiotensinogen in this model of hypertension. 29 It is interesting that normotensive CTL-TG in comparison with CTL-SD rats presented an increased ACE2 mRNA expression accompanied by similar levels of Ang-(1-7) and a tendency for lower Ang II levels in the LV. These data are consistent with those obtained in previous studies.…”

Section: Discussionmentioning

confidence: 93%

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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“…Cardiac hypertrophy and renal damage occur much more acutely in the DOCA-salt model. 14,15 In the present study, unilateral nephrectomy, subcutaneous administrations of DOCA, and subsequent salt loading were used to create the volume-overload hypertensive animal model. We explored the effects of a continuous supply of AM via a single intravenous injection of a replication-deficient adenovirus harboring the human AM gene in DOCA-salt hypertensive rats.…”

mentioning

confidence: 99%

Adrenomedullin Gene Delivery Attenuates Hypertension, Cardiac Remodeling, and Renal Injury in Deoxycorticosterone Acetate-Salt Hypertensive Rats

et al. 2000

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Abstract-Adrenomedullin (AM) is a potent vasodilator and natriuretic peptide that plays an important role in cardiorenal function. In this study, we explored the potential protective role of AM in volume-dependent hypertension by somatic gene delivery. Adenovirus containing the human AM cDNA under the control of the cytomegalovirus promoter/ enhancer was administered into deoxycorticosterone acetate (DOCA)-salt hypertensive rats via tail vein injection. A single injection of the human AM gene resulted in a prolonged reduction of blood pressure with a maximal reduction of 41 mm Hg 9 days after gene delivery. Human AM gene delivery enhanced renal function, as indicated by a 3-fold increase in renal blood flow and a 2-fold increase in glomerular filtration rate (nϭ5, PϽ0.05). Histological examination of the kidney revealed a significant reduction in glomerular sclerosis, tubular injury, luminol protein cast accumulation, and interstitial fibrosis as well as urinary protein. Human AM gene delivery caused significant decreases in left ventricular weight and cardiomyocyte diameter, which were accompanied by reduced interstitial fibrosis and extracellular matrix formation within the heart. Expression of human AM mRNA was detected in the kidney, adrenal gland, heart, aorta, lung, and liver; immunoreactive human AM levels were measured in urine and plasma. Significant increases in urinary and cardiac cAMP levels were observed in DOCA-salt rats receiving the human AM gene, indicating activation of the AM receptor. These findings showed that AM gene delivery attenuates hypertension, protects against cardiac remodeling and renal damage in volume-overload hypertension, and may have significance in therapeutic applications in cardiovascular and renal diseases.

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Myocardial renin is neither necessary nor sufficient to initiate or maintain ventricular hypertrophy

Cited by 11 publications

References 45 publications

Chronic infusion of angiotensin-(1-7) into the lateral ventricle of the brain attenuates hypertension in DOCA-salt rats

Chronic infusion of angiotensin-(1-7) into the lateral ventricle of the brain attenuates hypertension in DOCA-salt rats

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

Adrenomedullin Gene Delivery Attenuates Hypertension, Cardiac Remodeling, and Renal Injury in Deoxycorticosterone Acetate-Salt Hypertensive Rats

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