Effects of chronic hypoxia on the circulating and pancreatic renin-angiotensin system.
BACKGROUND
The circulating renin-angiotensin system (RAS) plays a crucial role in the regulation of blood pressure, electrolytes, and fluid homeostasis. In contrast to the circulating RAS, the presence of an intrinsic RAS has been demonstrated in different tissues/organs, which may affect both local and global functions of a biologic system. Our previous studies provided solid evidence of the existence of a local RAS in rat pancreas. Our further investigation showed that such a pancreatic RAS could be activated by experimental models of chronic hypoxia and chemically induced pancreatitis. These previous findings formed the basis for the current study.


METHODS
Adult Sprague-Dawley rats were exposed to isobaric hypoxia (10% O2), and the effects on the circulating and pancreatic RAS were documented.


RESULTS
The current study shows that exposure of rats to isobaric hypoxia caused a time-dependent increase in plasma renin activity. The activation of circulating RAS by hypoxia was associated with a parallel upregulation of local RAS components, including the mRNA expression of angiotensinogen and angiotensin II receptor types I and II in the pancreas.


CONCLUSIONS
The upregulation of local pancreatic RAS, along with its counterpart circulating RAS, may be responsible for both physiologic and pathophysiologic aspects of a biologic system under chronic hypoxic stress.
Ip
Siu Po
SP
Department of Physiology and School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong.
Chan
Yik Wai
YW
Leung
Po Sing
PS
D000808:Angiotensinogen / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002908:Chronic Disease; D000860:Hypoxia / Q000097:blood* / Q000378:metabolism*; D007700:Kinetics; D010179:Pancreas / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000235:genetics; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System; D015854:Up-Regulation
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D012083:Renin