Review: The practical aspects of combination therapy with angiotensin receptor blockers and angiotensin-converting enzyme inhibitors

Sica, Domenic A.

doi:10.3317/jraas.2002.020

Cited by 7 publications

(4 citation statements)

References 67 publications

(161 reference statements)

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“…27 The importance of the vasodeleterious axis of the RAS [ACE/Ang II/AT1R] in cardiovascular disease, as well as in diabetes and diabetic complications, is well established since ACEi and ARBs are leading therapeutic strategies. [29][30][31][32] However, the impact of the vasoprotective axis of the RAS remains poorly understood. 27,[33][34][35] The concept that shifting the balance of the RAS towards the vasodilatory axis by activation of ACE2 or its product, Ang-(1-7) is beneficial has been supported by many studies in cardiac, pulmonary, and vascular fibrosis.…”

Section: Introductionmentioning

confidence: 99%

ACE2 and Ang-(1-7) Confer Protection Against Development of Diabetic Retinopathy

et al. 2012

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Despite evidence that hyperactivity of the vasodeleterious axis (ACE/angiotensin II (Ang II)/AT1 receptor) of the renin-angiotensin system (RAS) is associated with the pathogenesis of diabetic retinopathy (DR) use of the inhibitors of this axis has met with limited success in the control of this pathophysiology. We investigated the hypothesis that enhancing the local activity of the recently established protective axis of the RAS, ACE2/Ang-(1-7), using adeno-associated virus (AAV)-mediated gene delivery of ACE2 or Ang-(1-7) would confer protection against diabetes-induced retinopathy. Genes expressing ACE2 and Ang-(1-7) were cloned in AAV vector. The effects of ocular AAV-ACE2/Ang-(1-7) gene transfer on DR in diabetic eNOS(-/-) mice and Sprague-Dawley (SD) rats were examined. Diabetes was associated with approximately tenfold and greater than threefold increases in the ratios of ACE/ACE2 and AT1R/Mas mRNA levels in the retina respectively. Intraocular administration of AAV-ACE2/Ang-(1-7) resulted in significant reduction in diabetes-induced retinal vascular leakage, acellular capillaries, infiltrating inflammatory cells and oxidative damage in both diabetic mice and rats. Our results demonstrate that DR is associated with impaired balance of retinal RAS. Increased expression of ACE2/Ang-(1-7) overcomes this imbalance and confers protection against DR. Thus, strategies enhancing the protective ACE2/Ang-(1-7) axis of RAS in the eye could serve as a novel therapeutic target for DR.

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Section: Introductionmentioning

confidence: 99%

ACE2 and Ang-(1-7) Confer Protection Against Development of Diabetic Retinopathy

et al. 2012

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“…This vasoprotective axis of RAS counteracts the traditional proliferative, fibrotic, proinflammatory and hypertrophic effects of the ACE/Ang II/AT1R axis of the RAS [24]. The importance of the vasodeleterious axis of the RAS [ACE/angiotensin II (Ang II)/ AT1R] in cardiovascular disease, as well as in diabetes and diabetic complications, is well established since ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are leading therapeutic strategies [20,[33][34][35]. However, the impact of the vasoprotective axis of the RAS remains poorly understood [24,[36][37][38].…”

Section: Recent Advances In Ras Researchmentioning

confidence: 99%

“…The importance of the vasodeleterious axis of the RAS (ACE/ Ang II/ AT1R) in cardiovascular disease, as well as in diabetes and diabetic complications, is well established since ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are leading therapeutic strategies [20,[33][34][35]. However, the impact of the vasoprotective axis of the RAS remains poorly understood, particularly in the eye.…”

Section: Possible Mechanisms Of Protective Action Of Ace2/ang (1-7) Imentioning

confidence: 99%

Gene Therapy for Diabetic Retinopathy – Targeting the Renin-Angiotensin System

Li¹,

Verma²,

Zhu³

et al. 2013

Gene Therapy - Tools and Potential Applications

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Additional information is available at the end of the chapter http://dx.doi.org/10.5772/52702 . Introduction . . Diabetic retinopathy clinical features and current treatment optionsThe prevalence of diabetes has been continuously increasing for the last few decades and it is being recognized as a worldwide epidemic [ ]. Diabetic retinopathy DR is the most common diabetic microvascular complication, and despite recent advances in therapeutics and management, DR remains the leading cause of severe vision loss in people under age of sixty [ -]. The prevalence of DR increases with duration of diabetes, and nearly all individuals with type diabetes and more than % of those with type have some form of retinopathy after years [ -].Diabetic retinopathy DR is characterized by the development of progressive pathological changes in the retinal neuro-glial cells and microvasculature. The earlier hallmarks of diabetic retinopathy include breakdown of the blood-retinal barrier BRB , loss of pericytes, thickening of basement membrane, and the formation of microaneuryms, which are outpouchings of capillaries [ ]. BRB breakdown results in increased vascular permeability and leakage of fluid into the macula causing macular edema, another significant cause of vision loss in those with diabetes. With the progression of diabetic retinopathy, hemorrhage, macular edema, cotton wool spots, all signs of retinal ischemia, and hard exudates, the result of precipitation of lipoproteins and other circulating proteins through abnormally leaky retinal vessels become increasingly apparent. More severe and later stages of diabetic retinopathy, known as proliferative diabetic retinopathy PDR , is char- acterized by pathological neovascularization. Vision loss can occur from vitreous hemorrhage or from tractional retinal detachment [ , ].Despite recent developments in the pharmacotherapy of DR, treatment options for patients with DR are still limited. Laser photocoagulation, the primary treatment option for patients with PDR, is still considered gold standard therapy for the treatment of PDR. Although this treatment slows the loss of vision in those with PDR, it does not represent a cure, and is in itself a cell destructive therapy. Corticosteroids and anti-VEGF agents have shown promising results with regard to prevention of neovascularization, but remain limited in use due to their short-duration effects. More importantly, none of these agents have been able to substitute for the durability and effectiveness of laser mediated panretinal photocoagulation in preventing vision loss in the late stages of DR. . . RAS and diabetic complicationsThe renin-angiotensin system RAS plays a vital role in the cardiovascular homeostasis by regulating vascular tone, fluid and electrolyte balance, and in the sympathetic nerve system. Angiotensin II Ang II , a peptide hormone of RAS, has been known to regulate a variety of hemodynamic physiological responses, including fluid homeostasis, renal function, and contraction of vascular smooth muscle [ ]. In addition,...

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“…The literature has suggested that the brain angiotensin system consisting of AII and AII receptors participates in the development and maintenance of hypertension in SHR rats. It is conceivable that the combination of an AT1 receptor antagonist with an ACE inhibitor represents an appealing therapeutic strategy [30].…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II Receptor Binding in the Locus ceruleus of Spontaneously Hypertensive Rats and Wistar-Kyoto Rats: A Quantitative Autoradiographic Study with References to Hypertension and Cardiac/Testicular Hypertrophy

2004

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The locus ceruleus (LC) contains a high density of angiotensin II (AII) receptors. The role of AII receptors at the LC in genetic hypertension and organ function is unclear. Spontaneously hypertensive (SHR) rats and Wistar-Kyoto (WKY) rats were studied, and blood pressure of animals was measured using the tail-cuff method. Animals were decapitated and the heart weight (HW) and testicular weight (TW) of animals measured. AII receptor binding was carried out by incubating the LC tissue sections with 200 pM [¹²⁵I]-AII receptor ligand, and measured using quantitative autoradiography. Results showed that the HW/BW ratio was significantly higher in SHR rats than WKY rats. However, the TW/BW ratio was higher in SHR rats than WKY rats only at two hypertensive stages, whereas AII receptor binding capacity in the LC was also statistically higher in SHR rats than WKY rats. Results indicated that cardiac and testicular hypertrophies were related to higher AII receptor binding in the LC of SHR rats, when compared with WKY rats. Interestingly, the literature shows that there is an LC-testes axis. In conclusion, this study indicated that AII receptors in the LC are associated with genetic hypertension, and testicular weight could be a reasonable index for essential hypertension.

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Review: The practical aspects of combination therapy with angiotensin receptor blockers and angiotensin-converting enzyme inhibitors

Cited by 7 publications

References 67 publications

ACE2 and Ang-(1-7) Confer Protection Against Development of Diabetic Retinopathy

ACE2 and Ang-(1-7) Confer Protection Against Development of Diabetic Retinopathy

Gene Therapy for Diabetic Retinopathy – Targeting the Renin-Angiotensin System

Angiotensin II Receptor Binding in the Locus ceruleus of Spontaneously Hypertensive Rats and Wistar-Kyoto Rats: A Quantitative Autoradiographic Study with References to Hypertension and Cardiac/Testicular Hypertrophy

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