Abstract

Angiotensin II (AngII) facilitates sympathetic neurotransmission by regulating norepinephrine (NE) synthesis, release, and uptake. These effects of AngII contribute to cardiovascular control. Previous studies in our laboratory demonstrated that chronic AngII infusion decreased body weight of rats. We hypothesized that AngII facilitates sympathetic neurotransmission to adipose tissue and may thereby decrease body weight. The effect of chronic AngII infusion on the NE uptake transporter and NE turnover was examined in metabolic (interscapular brown adipose tissue, ISBAT; epididymal fat, EF) and cardiovascular tissues (left ventricle, LV; kidney) of rats. To examine the uptake transporter saturation isotherms were performed using [3H]nisoxetine (NIS). At doses that lowered body weight, AngII significantly increased ISBAT [3H]NIS binding density. To quantify NE turnover, alpha-methyl-para-tyrosine (AMPT) was injected in saline-infused, AngII-infused, or saline-infused rats that were pair-fed to food intake of AngII-infused rats. AngII significantly increased the rate of NE decline in all tissues compared to saline. The rate of NE decline in EF was increased to a similar extent by AngII and by pair feeding. In rats administered AngII and propranolol, reductions in food and water intake and body weight were eliminated. These data support the hypothesis that AngII facilitates sympathetic neurotransmission to adipose tissue. Increased sympathetic neurotransmission to adipose tissue following AngII exposure is suggested to contribute to reductions in body weight.

Highlights

  • Angiotensin II (AngII), the primary peptide of the renin– angiotensin system (RAS) with biologic activity, is important in the regulation of arterial pressure and fluid and electrolyte balance (Peach 1981)

  • In all rats infused with AngII, food intake gradually returned toward control in a dose- and time-dependent manner

  • Elevations in catecholamine turnover in white and brown adipose tissue were demonstrated at doses of AngII that stimulated the turnover of NE in cardiovascular tissues and elevated plasma concentrations of free fatty acids

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Summary

Introduction

Angiotensin II (AngII), the primary peptide of the renin– angiotensin system (RAS) with biologic activity, is important in the regulation of arterial pressure and fluid and electrolyte balance (Peach 1981). The ability of adipocytes to synthesize components of the RAS raises the question of whether AngII acts locally to influence adipose tissue function. Recent studies from our laboratory demonstrated that deficiency of angiotensin type 1a receptors (AT1aR) in adipocytes of mice resulted in adipocyte hypertrophy in lean, but not in obese mice (Putnam et al 2012). These effects were linked to reductions in differentiation of adipocytes (Putnam et al 2012), suggesting that AngII influences fat mass.

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