title: Chronic hypoxia activates a local angiotensin-generating system in rat carotid body.
abstract: Evidence exists for the presence of a functional angiotensin system in the carotid body, which can modulate the excitability of the carotid body chemoreceptors. In the present study, the effect of chronic hypoxia on the expression and localization of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE), the two critical components of an intrinsic angiotensin-generating system in the rat carotid body, are investigated by in situ hybridization histochemistry, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. In situ hybridization showed that the messenger RNA (mRNA) expression of AGT was localized within the type-I glomus cells of the carotid body, which was subjected to be upregulated under the stress of chronic hypoxia. RT-PCR further confirmed a significant increase in the expression of AGT mRNA by chronic hypoxia. Consistently, Western blot analysis demonstrated that chronic hypoxia could elicit the upregulation of AGT protein in chronically hypoxic carotid bodies when compared with their normoxic controls. On the other hand, there was a slight but significant increase in ACE mRNA expression during chronic hypoxia. This study suggests that chronic hypoxia can activate a local angiotensin-generating system in the carotid body, notably its obligatory component AGT. The activation of such an intrinsic, angiotensin-generating system in the carotid body during chronic hypoxia should be important in the modulation of cardiopulmonary adaptation in the hypoxic ventilatory response and the electrolyte as well as water homeostasis.
authors.affiliation: Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Siu Yin
authors.initials: SY
authors.lastname: Lam
authors.forename: Po Sing
authors.initials: PS
authors.lastname: Leung
mesh_terms: D000222:Adaptation, Physiological; D000808:Angiotensinogen / Q000032:analysis / Q000235:genetics; D000809:Angiotensins / Q000032:analysis / Q000235:genetics*; D000818:Animals; D002344:Carotid Body / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000378:metabolism; D002908:Chronic Disease; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D000809:Angiotensins; D012333:RNA, Messenger; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A