The natriuretic peptide system in obesity-related hypertension: new pathophysiological aspects

The association between obesity and hypertension is well known but the path ophysiology of weight-related changes on blood pressure is still a matter o f debate. Although obesity-related hypertension is considered to be sodium- sensitive, little attention has been given to a possible pathophysiological role of Atrial Natriuretic Peptides (ANP) and their receptors (NPr) system . Since the early phase of weight loss induced by very-low-calorie diet or fasting is followed by a significant increase in diuresis and natriuresis t ogether with an increase in circulating ANP, we focused our attention on th e possible role of adipose tissue in mediating these changes. We first demo nstrated that human and rat adipose tissue contain high levels of mRNA spec ific for both type A (NPr-A), which is biologically active, and type C (NPr -C) which is biologically inactive, receptors. We then demonstrated in the rat that fasting exerts a tissue-specific and gem-specific suppression of N Pr-C gene expression in adipose tissue that appears to be accompanied by an increased biological activity of ANP. These experimental observations were confirmed in man studying gene expression of NPr-A and NPr-C in adipose ti ssue obtained through subcutaneous peri-umbilical needle aspiration in obes e and non-obese hypertensive patients. We found that NPr-A: NPr-C mRNA rati o was significantly lower in obese hypertensive patients as compared with n on-obese hypertensives. These findings suggest that overexpression of the c learance receptor in the obese may trap more molecules of circulating ANP s o reducing their biological activity at renal level. More recent results we re obtained in obese hypertensive patients in whom the intravenous bolus in jection of ANP (0.6 mg/kg body weight) was performed before and after four days of very-low-calorie diet which induced a weight loss accompanied by a significant reduction of BP and an increase in the urinary excretion of cGM P. The infusion of ANP after low-calorie diet was followed by an increase o f ANP levels similar to that observed before diet, but plasma cGMP, diuresi s and natriuresis significantly increased only after caloric restriction an d the effects of ANP infusion on BP were more pronounced. Taken together ou r studies suggest that the abundance of NPr-C in adipose tissue may play a significant role in explaining at least part of the sodium retention charac teristic of obesity associated hypertension.