Role of central angiotensin II receptors in cold-induced hypertension.
BACKGROUND
Earlier studies from this laboratory showed that central angiotensin II (AngII) receptors are upregulated by chronic cold exposure. The purpose of this study was to determine whether central AngII receptors may play a role in the development of cold-induced hypertension.


METHODS
Four groups of rats (six rats each) were used. Two groups were exposed to cold (5 degrees C) and the other two groups were kept at 25 degrees C. One cold-exposed and one warm-adapted group were treated chronically, via osmotic minipumps, with AngII type 1 (AT1) receptor blocker (losartan, 6.0 microg/2.5 microL/h, intracerebroventricularly) at the beginning of cold exposure.


RESULTS
Systolic blood pressure (BP) of the cold-exposed untreated group increased during week 1 of cold exposure and rose to 160+/-4 mm Hg by week 4, whereas BP of the losartan-treated group in cold did not increase and remained at 121+/-3 mm Hg. Cold-induced increases in drinking response to AngII, plasma renin activity, and urine norepinephrine output disappeared in the treated rats, indicating blockade of central AngII receptors. Withdrawal of losartan at 4 weeks resulted in an increase in BP of this group to the cold-exposed untreated level, which was accompanied by an increase in the above parameters. Significant increases in AngII-induced drinking response and hypothalamic AT1 receptor mRNA content of the cold-exposed rats indicate upregulation of AngII receptors during chronic cold exposure. Hypothalamic AngII level was not affected by cold exposure.


CONCLUSIONS
Upregulation of brain AT1 receptors plays a role in the development of cold-induced hypertension.
Sun
Zhongjie
Z
Department of Medicine, University of Florida, Gainesville 32610-0274, USA. zsun@phys.med.ufl.edu
Cade
Robert
R
Morales
Cerinda
C
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003080:Cold Temperature; D004327:Drinking Behavior / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D007276:Injections, Intraventricular; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000652:urine; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000378:metabolism; D012083:Renin / Q000097:blood; D015854:Up-Regulation / Q000502:physiology
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D012083:Renin; D019808:Losartan; D009638:Norepinephrine