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.
Conclusion: Upregulation of brain AT1 receptors plays a role in the development of cold-induced hypertension.