Phosphodiesterase 5 inhibitor ameliorates renal resistance to atrial natriuretic peptide associated with obesity and hyperleptinemia
Abstract
Abnormal neurohormonal regulation of renal sodium handling plays an important role in obesity-associated hypertension. We investigated the effect of experimental obesity on renal response to atrial natriuretic peptide (ANP). The effect of ANP was studied in three groups of rats: (1) lean controls, (2) animals made obese by a highly palatable diet, (3) rats treated with adipose tissue hormone, leptin, for 7 days to reproduce hyperleptinemia observed in obesity. ANP administered at a dose of 50 pmol/kg min(-1) induced about a 3-fold lower increase in Na+ and cGMP excretion in obese and leptin-treated rats than in the control group. ANP decreased Na+,K+-ATPase activity in the renal medulla only in the control group. Natriuretic effect of exogenous cGMP was also impaired in obese and leptin-treated rats. In contrast, hydrolysis-resistant cGMP derivative, 8-bromo-cGMP exerted comparable natriuretic effects in all groups. Neutral endopeptidase inhibitor, phosphoramidon, and ANP clearance receptor antagonist, C-ANP, increased urinary ANP excretion in all groups to a similar level, but their natriuretic effect was impaired in obese and leptin-treated groups. A specific inhibitor of cGMP-degrading phosphodiesterase, zaprinast, had compa...Continue Reading
References
Cyclic-3',5'-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney
Citations
Salt Intake, Aldosterone Secretion, and Obesity: Role in the Pathogenesis of Resistant Hypertension.
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