Sympathetic Modulation by Carvedilol and Losartan Reduces Angiotensin II-Mediated Lipolysis in Subcutaneous and Visceral Fat

Author:

Cabassi Aderville1,Coghi Pietro1,Govoni Paolo2,Barouhiel Elisa1,Speroni Ester3,Cavazzini Stefania4,Cantoni Anna Maria5,Scandroglio Renato2,Fiaccadori Enrico1

Affiliation:

1. Laboratory of Clinical Physiology, Hypertension Unit (A.C., P.C., E.B., E.F.), 43100 Parma, Italy

2. Section of Histology and Embryology, Department of Experimental Medicine (P.G., R.S.), 43100 Parma, Italy

3. Department of Pharmacology (E.S.), Faculty of Pharmacy, University of Bologna, 40126 Bologna, Italy

4. Toxicology Unit (S.C.), Department of Internal Medicine, Nephrology, and Health Sciences, 43100 Parma, Italy

5. Veterinary Pathology Unit (A.M.C.), Department of Animal Health, University of Parma Faculty of Veterinary Medicine, 43100 Parma, Italy

Abstract

Advanced heart failure is characterized by increased activation of the renin-angiotensin system and the development of cachexia. Angiotensin II (Ang II) has been proposed as a lipid metabolism regulator. The effects of exogenous Ang II (osmotic minipump, 525 ng/kg/min for 12 d) on interstitial sc glycerol and norepinephrine levels, indexes of lipolysis, and sympathetic activation, respectively, were measured in Sprague Dawley rats by consecutive microdialysis performed in vivo in white adipose tissue. Higher sustained interstitial glycerol and norepinephrine levels were found after 7 and 12 d of Ang II infusion. Triglyceride to DNA content ratio and adipocyte diameter were reduced in sc and visceral (retroperitoneal and epididymal) fat tissues of Ang II-infused rats, whose body weight was lower and blood pressure higher. Losartan, an Ang II receptor 1 blocker, and carvedilol, an α1-nonselective-β1,2,3-adrenergic blocker, but not doxazosin, an α1-selective-adrenergic blocker, lowered glycerol and norepinephrine levels, preventing lipolysis and weight loss. Our results indicate that Ang II stimulates lipolysis in sc and visceral adipocytes by sympathetic activation and β-adrenergic-receptor stimulation. Nonselective-β-adrenergic and Ang II-receptor1 blockade markedly attenuated the rise of norepinephrine, preventing catabolic effects. The metabolic benefits of carvedilol and losartan, in addition to recognized protective cardiovascular effects, may be relevant in cachectic patients with advanced heart failure.

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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