| Chronic Activation of Endogenous Angiotensin-Converting Enzyme 2 Protects Diabetic Rats from Cardiovascular Autonomic Dysfunction. | |
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MedLine Citation:
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PMID: 22286369 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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In this study we evaluated whether the activation of endogenous angiotensin-converting enzyme (ACE) 2 would improve the cardiovascular autonomic dysfunction of diabetic rats. Ten days after type 1 diabetes induction (Streptozotocin, STZ, 50mg/kg i.v.), the rats were orally treated with 1-[(2-dimethylamino)ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthene-9-one (XNT), a newly discovered ACE2 activator (1mg/kg/day), or saline (equivalent volume) during 30 days. Autonomic cardiovascular parameters were evaluated in unanesthetized animals and an isolated heart preparation was used to analyze the cardiac function. Diabetes induced a significant decrease in the baroreflex bradycardia sensibility, as well as in the chemoreflex chronotropic response and parasympathetic tone. The XNT treatment improved these parameters by ~76% (0.82±0.09 vs. 1.44±0.17ΔPI/ΔmmHg), ~85% (-57±9 vs. -105±10 Δbpm) and ~205% (22±2 vs. 66±12 Δbpm), respectively. Also, XNT administration enhanced the bradycardia induced by the chemoreflex activation by ~74% in non-diabetic animals (-98±16 vs. -170±9 Δbpm). No significant changes were observed in the mean arterial pressure, baroreflex tachycardia sensibility, 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 evidenced 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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Authors:
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Tatiane M Murça; Tatiane Cs Almeida; Mohan K Raizada; Anderson J Ferreira |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-27 |
Journal Detail:
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Title: Experimental physiology Volume: - ISSN: 1469-445X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9002940 Medline TA: Exp Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Federal University of Minas Gerais; |
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