COLD-EXPOSURE REGULATES THE RENIN-ANGIOTENSIN SYSTEM

The effect of cold exposure on the systemic renin-angiotensin system a nd on regulation of the angiotensin II (Ang II) receptor was examined in target organs for Ang II with cardiovascular relevance (left ventri cle, kidney, lung) and metabolic relevance [interscapular brown adipos e tissue (ISBAT), liver] to the functional consequences of cold exposu re. In time course studies, the effects were examined of 4 hr or 1, 3 and 7 days of exposure to cold (4 degrees C) on plasma Ang fl concentr ation and Ang II receptor binding characteristics in rat liver. Plasma Ang II concentration increased 10-fold after 4 hr of cold exposure, r eturned to control levels at days 1 and 3 of cold exposure, and was ag ain increased g-fold) at 7 days of cold exposure. The affinity of [I-1 25]Sar(1),Ile(8)-Ang II binding in membranes prepared from rat liver w as not altered in cold-exposed rats. The density (B-max) of binding si tes in liver from cold-exposed rats was increased by day 1 and remaine d elevated over time-matched controls. Alterations in Ang II receptor density did not parallel plasma Ang II concentration in their time cou rse, suggesting that cold-induced regulation of the Ang II receptor wa s not substrate mediated. In rats from the 7-day time point of cold ex posure, Ang It receptor binding characteristics were examined in ISBAT and lung. Increases in Ang II receptor density were evident in ISBAT but not lung. To determine whether cold-induced increases in food inta ke contributed to elevations in plasma Ang II concentration and/or Ang II receptor density, a group of cold-exposed rats (7 days) were pair- fed to food intake levels of control rats. Pair-feeding of cold-expose d rats eliminated increases in plasma Ang II and norepinephrine concen tration but did not prevent increases in Ang II receptor density in li ver, ISBAT, kidney and left ventricle. Moreover, increases in Ang II r eceptor density were augmented in kidney and left ventricle from cold- exposed rats that were pair-fed. Results from these studies demonstrat e that cold exposure resulted in an increase in plasma Ang II concentr ation through mechanisms related to increased food intake. Elevations in food intake in cold-exposed rats contributed to tissue-specific inc reases in Ang II receptor density. Moreover, cold-induced increases in Ang II receptor density were not related to plasma Ang II concentrati on.