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Article: Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes

TitleIncreased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes
Authors
Issue Date2005
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/
Citation
American Journal Of Physiology - Heart And Circulatory Physiology, 2005, v. 289 n. 5 58-5, p. H2144-H2152 How to Cite?
AbstractStudies in streptozotocin (STZ)-induced diabetic rats have demonstrated cardiovascular abnormalities such as depressed mean arterial blood pressure (MABP) and heart rate (HR), endothelial dysfunction, and attenuated pressor responses to vasoactive agents. We investigated whether these abnormalities are due to diabetes-associated activation of inducible nitric oxide synthase (iNOS). In addition, the effect of the duration of diabetes on these abnormalities was also evaluated. Diabetes was induced by administration of 60 mg/kg STZ via the tail vein. One, 3, 9, or 12 wk after STZ injection, MABP, HR, and endothelial function were measured in conscious unrestrained rats. Pressor response curves to bolus doses of methoxamine (MTX) and angiotensin II (ANG II) were constructed in the presence of N-[3(aminomethyl)benzyl]-acetamidine, dihydrochloride (1400W), a specific inhibitor of iNOS. Depressed MABP and HR and impairment of endothelial function were observed as early as 3 wk after induction of diabetes. Acute inhibition of iNOS with 1400W (3 mg/kg iv) restored the attenuated pressor responses to both MTX and ANG II without affecting the basal MABP and HR. Immunohistochemical and Western analysis blot studies in cardiovascular tissues revealed decreased expression of endothelial nitric oxide synthase (eNOS) concomitant with increased expression of iNOS and nitrotyrosine with the progression of diabetes. Our findings suggest that induction of iNOS in cardiovascular tissues is dependent on the duration of diabetes and contributes significantly to the depressed pressor responses to vasoactive agents and potentially to endothelial dysfunction. Copyright © 2005 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/147220
ISSN
2015 Impact Factor: 3.324
2015 SCImago Journal Rankings: 1.823
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNagareddy, PRen_US
dc.contributor.authorXia, Zen_US
dc.contributor.authorMcneill, JHen_US
dc.contributor.authorMacleod, KMen_US
dc.date.accessioned2012-05-29T06:00:52Z-
dc.date.available2012-05-29T06:00:52Z-
dc.date.issued2005en_US
dc.identifier.citationAmerican Journal Of Physiology - Heart And Circulatory Physiology, 2005, v. 289 n. 5 58-5, p. H2144-H2152en_US
dc.identifier.issn0363-6135en_US
dc.identifier.urihttp://hdl.handle.net/10722/147220-
dc.description.abstractStudies in streptozotocin (STZ)-induced diabetic rats have demonstrated cardiovascular abnormalities such as depressed mean arterial blood pressure (MABP) and heart rate (HR), endothelial dysfunction, and attenuated pressor responses to vasoactive agents. We investigated whether these abnormalities are due to diabetes-associated activation of inducible nitric oxide synthase (iNOS). In addition, the effect of the duration of diabetes on these abnormalities was also evaluated. Diabetes was induced by administration of 60 mg/kg STZ via the tail vein. One, 3, 9, or 12 wk after STZ injection, MABP, HR, and endothelial function were measured in conscious unrestrained rats. Pressor response curves to bolus doses of methoxamine (MTX) and angiotensin II (ANG II) were constructed in the presence of N-[3(aminomethyl)benzyl]-acetamidine, dihydrochloride (1400W), a specific inhibitor of iNOS. Depressed MABP and HR and impairment of endothelial function were observed as early as 3 wk after induction of diabetes. Acute inhibition of iNOS with 1400W (3 mg/kg iv) restored the attenuated pressor responses to both MTX and ANG II without affecting the basal MABP and HR. Immunohistochemical and Western analysis blot studies in cardiovascular tissues revealed decreased expression of endothelial nitric oxide synthase (eNOS) concomitant with increased expression of iNOS and nitrotyrosine with the progression of diabetes. Our findings suggest that induction of iNOS in cardiovascular tissues is dependent on the duration of diabetes and contributes significantly to the depressed pressor responses to vasoactive agents and potentially to endothelial dysfunction. Copyright © 2005 the American Physiological Society.en_US
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/en_US
dc.relation.ispartofAmerican Journal of Physiology - Heart and Circulatory Physiologyen_US
dc.subject.meshAmidines - Pharmacologyen_US
dc.subject.meshAngiotensin Ii - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBenzylamines - Pharmacologyen_US
dc.subject.meshBlood Pressure - Drug Effects - Physiologyen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshDiabetes Mellitus, Experimental - Enzymology - Physiopathologyen_US
dc.subject.meshEndothelium, Vascular - Physiologyen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshHeart Rate - Drug Effectsen_US
dc.subject.meshHemodynamics - Drug Effects - Physiologyen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshMaleen_US
dc.subject.meshMethoxamine - Pharmacologyen_US
dc.subject.meshNg-Nitroarginine Methyl Ester - Pharmacologyen_US
dc.subject.meshNeurotensin - Physiologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Wistaren_US
dc.subject.meshVascular Diseases - Physiopathologyen_US
dc.subject.meshVasoconstrictor Agents - Pharmacologyen_US
dc.titleIncreased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetesen_US
dc.typeArticleen_US
dc.identifier.emailXia, Z:zyxia@hkucc.hku.hken_US
dc.identifier.authorityXia, Z=rp00532en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1152/ajpheart.00591.2005en_US
dc.identifier.pmid16006542-
dc.identifier.scopuseid_2-s2.0-27144500956en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-27144500956&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume289en_US
dc.identifier.issue5 58-5en_US
dc.identifier.spageH2144en_US
dc.identifier.epageH2152en_US
dc.identifier.isiWOS:000232497500047-
dc.publisher.placeUnited Statesen_US
dc.identifier.f10001027594-

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