ArticleExperimental physiology2012
Chronic activation of endogenous angiotensin-converting enzyme 2 protects diabetic rats from cardiovascular autonomic dysfunction.
Article in Experimental physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
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- Altered Heart Rate Variability Early in ICU Admission Differentiates Critically Ill Coronavirus Disease 2019 and All-Cause Sepsis Patients.Critical care explorations · 2021Article
- An update on ACE2 amplification and its therapeutic potential.Acta physiologica (Oxford, England) · 2021Review
- Angiotensin-(1-7) Expressed From Lactobacillus Bacteria Protect Diabetic Retina in Mice.Translational vision science & technology · 2020Article
- Stimulation of the ACE2/Ang-(1-7)/Mas axis in hypertensive pregnant rats attenuates cardiovascular dysfunction in adult male offspring.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- New agents modulating the renin-angiotensin-aldosterone system-Will there be a new therapeutic option?Experimental biology and medicine (Maywood, N.J.) · 2016Review
- Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure.Circulation research · 2016Review
- High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia.Journal of diabetes research · 2016Article
- Activation of endogenous angiotensin converting enzyme 2 prevents early injuries induced by hyperglycemia in rat retina.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2015Article
- Combination of angiotensin-(1-7) with perindopril is better than single therapy in ameliorating diabetic cardiomyopathy.Scientific reports · 2015Article
- Angiotensin-converting enzyme 2-independent action of presumed angiotensin-converting enzyme 2 activators: studies in vivo, ex vivo, and in vitro.Hypertension (Dallas, Tex. : 1979) · 2014Article
- Angiotensin-converting enzyme 2 activation improves endothelial function.Hypertension (Dallas, Tex. : 1979) · 2013Article
- Opportunities for targeting the angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor pathway in hypertension.Current hypertension reports · 2013Review
- Key developments in renin-angiotensin-aldosterone system inhibition.Nature reviews. Nephrology · 2013Review
- Oral administration of an angiotensin-converting enzyme 2 activator ameliorates diabetes-induced cardiac dysfunction.Regulatory peptides · 2012Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
In this study, we evaluated whether the activation of endogenous angiotensin-converting enzyme 2 (ACE2) would improve the cardiovascular autonomic dysfunction of diabetic rats. Ten days after induction of type 1 diabetes (streptozotocin, 50 mg kg(-1) i.v.), the rats were treated orally with 1-[(2-dimethylamino)ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthene-9-one (XNT), a newly discovered ACE2 activator (1 mg kg(-1) day(-1)), or saline (equivalent volume) for 30 days. Autonomic cardiovascular parameters were evaluated in conscious animals, and an isolated heart preparation was used to analyse cardiac function. Diabetes induced a significant decrease in the baroreflex bradycardia sensitivity, as well as in the chemoreflex chronotropic response and parasympathetic tone. The XNT treatment improved these parameters by ≈ 76% [0.82 ± 0.09 versus 1.44 ± 0.17 Ratio between changes in pulse interval and changes in mean arterial pressure (ΔPI/ΔmmHg)], ∼85% (-57 ± 9 versus -105 ± 10 beats min(-1)) and ≈ 205% (22 ± 2 versus 66 ± 12 beats min(-1)), respectively. Also, XNT administration enhanced the bradycardia induced by the chemoreflex activation by v 74% in non-diabetic animals (-98 ± 16 versus -170 ± 9 Δbeats min(-1)). No significant changes were observed in the mean arterial pressure, baroreflex tachycardia sensitivity, chemoreflex pressor response and sympathetic tone among any of the groups. Furthermore, chronic XNT treatment ameliorated the cardiac function of diabetic animals. However, the coronary vasoconstriction observed in diabetic rats was unchanged by ACE2 activation. These findings indicate that XNT protects against the autonomic and cardiac dysfunction induced by diabetes. Thus, our results provide evidence for the viability and effectiveness of oral administration of an ACE2 activator for the treatment of the cardiovascular autonomic dysfunction caused by diabetes.
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