Angiotensin II enhances the release of catecholamine neurotransmitters throughout the central and peripheral nervous system. Norepinephrine (NE) is the major catecholamine neurotransmitter in interscapular brown adipose tissue (ISBAT), an important organ for nonshivering thermogenesis. Alterations in ISBAT function are related to the development of obesity. Preliminary studies demonstrate that cold-induced thermogenesis results in increases in AII content and AII enhancement of evoked NE release in ISBAT. Alterations in sympathetic neurotransmission in ISBAT following cold-exposure include increases in basal NE release, and decreased neuronal uptake of NE. Evidence for an endogenous renin-angiotensin system in ISBAT include immunoreactive AII in tissue extracts and extracellular fluid, angiotensinogen (Aogen) messenger RNA (mRNA) expression, and renin-like activity. Proposed studies will use ISBAT as a model system to examine interactions between the sympathetic nervous system and a functional, endogenous tissue renin-angiotensin system (RAS). The working hypothesis of this revised proposal is that endogenously produced AII in ISBAT is a primary mediator of enhanced sympathetic neurotransmission in cold-induced thermogenesis. Mechanism(s) for increased sympathetic neurotransmission in ISBAT in response to cold-exposure will be determined by examining the time course for development of alterations in basal NE release and neuronal uptake, for alterations in AII content and AII-modulation of NE release. Kinetic parameters for the neuronal uptake transporter will be examined. The cellular pool contributing to increases in basal NE release, and the metabolic profile for catecholamine release will be examined. Mechanisms for cold-induced regulation of the ISBAT renin- angiotensin system will be identified by defining mRNA expression of AII synthetic components, AII turnover, enzymatic activity of AII processing enzymes and metabolism of AII. Interactions between AII and increased sympathetic neurotransmission in ISBAT from cold- exposed rats will be examined. Therefore, proposed studies will use a comprehensive multi- disciplinary approach to determine interactions between a functional, endogenous RAS and sympathetic neurotransmission. The health relatedness of this proposal is that interactions between AII and NE in ISBAT may play a role in the altered adipose tissue metabolism of obesity and obesity-related hypertension.
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| Cassis, L; Laughter, A; Fettinger, M et al. (1998) Cold exposure regulates the renin-angiotensin system. J Pharmacol Exp Ther 286:718-26 |
| Shenoy, U; Cassis, L (1997) Characterization of renin activity in brown adipose tissue. Am J Physiol 272:C989-99 |
