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Article: Postnatal hypoxemia increases angiotensin II sensitivity and up-regulates AT 1a angiotensin receptors in rat carotid body chemoreceptors

TitlePostnatal hypoxemia increases angiotensin II sensitivity and up-regulates AT 1a angiotensin receptors in rat carotid body chemoreceptors
Authors
Issue Date2002
PublisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.org
Citation
Journal Of Endocrinology, 2002, v. 173 n. 2, p. 305-313 How to Cite?
AbstractIn the present study, the effects of postnatal hypoxemia on the AT 1 angiotensin receptor-mediated activities in the rat carotid body were studied. Angiotensin II (Ang II) concentration-dependently increased the chemoreceptor afferent activity in the isolated carotid body. Single- or pauci-fiber recording of the sinus nerve revealed that the afferent response to Ang II was enhanced in the postnatally hypoxic carotid body. To determine whether the increased sensitivity to Ang II is mediated by changes in the functional expression of Ang II receptors in the carotid body chemoreceptors, cytosolic calcium ([Ca 2+]i) was measured by spectrofluorimetry in fura-2 acetoxymethyl ester-loaded type I cells dissociated from carotid bodies. Ang II (25-100 nM) concentration-dependently increased [Ca 2+]i in the type I cells. The proportion of clusters of type I cells responsive to Ang II was higher in the postnatally hypoxic group than in the normoxic control (89 vs 66%). In addition, the peak [Ca 2+]i response to Ang II was enhanced 2- to 3-fold in the postnatally hypoxic group. The [Ca 2+]i response to Ang II was abolished by pretreatment with losartan (1 μM), an AT 1 receptor antagonist, but not by PD-123177 (1 μM), an AT 2 antagonist. Double-labeling immunohistochemistry confirmed that an enhanced immunoreactivity for AT 1 receptor was co-localized to the lobules of type I cells in the hypoxic group. In addition, RT-PCR analysis of subtypes of AT 1 receptors showed an up-regulation of AT 1a but a down-regulation of AT 1b receptors, indicating a differential regulation of the expression of AT 1 receptor subtypes by postnatal hypoxia in the carotid body. These data suggest that postnatal hypoxemia is associated with an increased sensitivity of peripheral chemoreceptors in response to Ang II and an up-regulation of AT 1a receptor-mediated [Ca 2+]i activity of the chemoreceptors. This modulation may be important for adaptation of carotid body functions in the hypoxic ventilatory response and in electrolyte and water homeostasis during perinatal and postnatal hypoxia.
Persistent Identifierhttp://hdl.handle.net/10722/171704
ISSN
2015 Impact Factor: 4.498
2015 SCImago Journal Rankings: 1.910
References

 

DC FieldValueLanguage
dc.contributor.authorFung, MLen_US
dc.contributor.authorLam, SYen_US
dc.contributor.authorDong, Xen_US
dc.contributor.authorChen, Yen_US
dc.contributor.authorLeung, PSen_US
dc.date.accessioned2012-10-30T06:16:30Z-
dc.date.available2012-10-30T06:16:30Z-
dc.date.issued2002en_US
dc.identifier.citationJournal Of Endocrinology, 2002, v. 173 n. 2, p. 305-313en_US
dc.identifier.issn0022-0795en_US
dc.identifier.urihttp://hdl.handle.net/10722/171704-
dc.description.abstractIn the present study, the effects of postnatal hypoxemia on the AT 1 angiotensin receptor-mediated activities in the rat carotid body were studied. Angiotensin II (Ang II) concentration-dependently increased the chemoreceptor afferent activity in the isolated carotid body. Single- or pauci-fiber recording of the sinus nerve revealed that the afferent response to Ang II was enhanced in the postnatally hypoxic carotid body. To determine whether the increased sensitivity to Ang II is mediated by changes in the functional expression of Ang II receptors in the carotid body chemoreceptors, cytosolic calcium ([Ca 2+]i) was measured by spectrofluorimetry in fura-2 acetoxymethyl ester-loaded type I cells dissociated from carotid bodies. Ang II (25-100 nM) concentration-dependently increased [Ca 2+]i in the type I cells. The proportion of clusters of type I cells responsive to Ang II was higher in the postnatally hypoxic group than in the normoxic control (89 vs 66%). In addition, the peak [Ca 2+]i response to Ang II was enhanced 2- to 3-fold in the postnatally hypoxic group. The [Ca 2+]i response to Ang II was abolished by pretreatment with losartan (1 μM), an AT 1 receptor antagonist, but not by PD-123177 (1 μM), an AT 2 antagonist. Double-labeling immunohistochemistry confirmed that an enhanced immunoreactivity for AT 1 receptor was co-localized to the lobules of type I cells in the hypoxic group. In addition, RT-PCR analysis of subtypes of AT 1 receptors showed an up-regulation of AT 1a but a down-regulation of AT 1b receptors, indicating a differential regulation of the expression of AT 1 receptor subtypes by postnatal hypoxia in the carotid body. These data suggest that postnatal hypoxemia is associated with an increased sensitivity of peripheral chemoreceptors in response to Ang II and an up-regulation of AT 1a receptor-mediated [Ca 2+]i activity of the chemoreceptors. This modulation may be important for adaptation of carotid body functions in the hypoxic ventilatory response and in electrolyte and water homeostasis during perinatal and postnatal hypoxia.en_US
dc.languageengen_US
dc.publisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.orgen_US
dc.relation.ispartofJournal of Endocrinologyen_US
dc.rightsJournal of Endocrinology. Copyright © Society for Endocrinology.-
dc.subject.meshAngiotensin Ii - Pharmacologyen_US
dc.subject.meshAngiotensin Receptor Antagonistsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnimals, Newbornen_US
dc.subject.meshAnoxia - Metabolismen_US
dc.subject.meshCalcium - Metabolismen_US
dc.subject.meshCarotid Body - Metabolismen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshImidazoles - Pharmacologyen_US
dc.subject.meshLosartan - Pharmacologyen_US
dc.subject.meshModels, Animalen_US
dc.subject.meshPyridines - Pharmacologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReceptor, Angiotensin, Type 1en_US
dc.subject.meshReceptor, Angiotensin, Type 2en_US
dc.subject.meshReceptors, Angiotensin - Metabolismen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSpectrometry, Fluorescenceen_US
dc.titlePostnatal hypoxemia increases angiotensin II sensitivity and up-regulates AT 1a angiotensin receptors in rat carotid body chemoreceptorsen_US
dc.typeArticleen_US
dc.identifier.emailFung, ML:fungml@hkucc.hku.hken_US
dc.identifier.authorityFung, ML=rp00433en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1677/joe.0.1730305en_US
dc.identifier.pmid12010638-
dc.identifier.scopuseid_2-s2.0-0036099094en_US
dc.identifier.hkuros81748-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036099094&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume173en_US
dc.identifier.issue2en_US
dc.identifier.spage305en_US
dc.identifier.epage313en_US
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridFung, ML=7101955092en_US
dc.identifier.scopusauthoridLam, SY=7402279518en_US
dc.identifier.scopusauthoridDong, X=55184171400en_US
dc.identifier.scopusauthoridChen, Y=24075600300en_US
dc.identifier.scopusauthoridLeung, PS=7401748938en_US

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