Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice

Objective Recent advances in understanding the neuroendocrine pathways regu lating appetite, metabolism and body weight afford an opportunity to explor e further the mechanisms by which obesity influences arterial pressure. ob/ ob(Lep(ob)/Lep(ob)) mice have a mutation in the oh gene and are leptin-defi cient. Leptin possesses presser actions and has been shown to increase arte rial pressure when infused chronically or over-expressed transgenically. In contrast, agouti yellow obese(A(y)) mice have overexpression of an agouti peptide that blocks melanocortin receptors. Stimulation of melanocortin rec eptors by alpha-melanocyte-stimulating hormone decreases arterial pressure. Design and methods This study measured arterial pressure in leptin-deficien t ob/ob mice, agouti yellow obese mice and their lean controls to test the hypothesis that the effects of obesity on arterial pressure are importantly influenced by the genetic and neuroendocrine mechanisms causing the obesit y. We measured arterial pressure directly in conscious ob/ob mice (n =14), agouti yellow obese mice (n = 6) and the same number of lean littermates. Results Body weight was nearly twice as high in ob/ob mice as in their lean controls, but mean arterial pressure was significantly lower in ob/ob mice (92 +/- 3 mmHg) compared with their lean controls (106 +/- 2 mmHg; P = 0.0 0017). In contrast, mean arterial pressure was significantly higher in agou ti yellow obese mice (124 a 3 mmHg) than in their lean controls (99 +/- 1 m mHg; P = 0.000002) despite the fact that the agouti mice had milder obesity . Conclusions This study prompts three conclusions: (1) leptin-deficient ob/o b mice and agouti yellow obese mice have contrasting blood pressure respons es to obesity, (2) obesity does not invariably increase arterial pressure i n mice, and (3) the arterial pressure response to obesity may depend critic ally on the underlying genetic and neuroendocrine mechanisms. (C) Lippincot t Williams & Wilkins.