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Elevated renin and enhanced adrenal steroidogenesis in the Ossabaw swine model of the metabolic syndrome
Author(s) -
Aloosh Mouhamad,
Pratt J. Howard,
Sturek Michael,
Basile David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.736.7
Subject(s) - medicine , endocrinology , aldosterone , metabolic syndrome , dyslipidemia , insulin resistance , renal function , renin–angiotensin system , angiotensin ii , plasma renin activity , creatinine , obesity , blood pressure
The Ossabaw pig fed an atherogenic diet develops features of the metabolic syndrome (MetS). We hypothesized that development of MetS in Ossabaw swine would result in increased activation of the renin‐angiotensin aldosterone system (RAAS) and development of hypertension. Male Ossabaw swine (∼20 weeks age) were fed excess atherogenic diet for 55 weeks, resulting in robust MetS characterized by obesity, insulin resistance, dyslipidemia and hypertension. Serum creatinine and urea nitrogen levels were reduced in MetS vs lean controls (∼13 and 48 %, p<0.05), suggesting renal hyperfiltration. Plasma renin activity in fasting, unstressed animals was higher (0.5 ± 0.2 vs 2.9 ± 0.5 ng Ang I ·ml−1· min−1) in MetS pigs relative to lean controls. Aldosterone levels were also elevated ∼6‐fold in MetS pigs. An additional group of pigs fed atherogenic diet for 9 weeks was used to measure adrenal responsiveness in early MetS. Ang II (5 ng·kg−1·min−1) or ACTH (2 ng ·kg−1·min−1) infusion into conscious MetS pigs resulted in significantly greater peak aldsosterone secretion relative to lean controls. Taken together, the data suggest that the development of MetS in Oss pigs leads to an alteration in renal function and renin and aldosterone secretion are enhanced in this setting; the latter may be secondary to increased Ang II and possibly increased adrenocortical sensitivity.(Support: NIH RR013223 , HL062552 ).