Dessì-Fulgheri P, Sarzani R, Rappelli A
Istituto di Medicina Clinica, Cattedra di Medicina Interna I University of Ancona, Italy.
J Nephrol. 1998 Nov-Dec;11(6):296-9.
The association between obesity and hypertension is well known but the pathophysiology of weight-related changes on blood pressure is still a matter of 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 together with an increase in circulating ANP, we focused our attention on the possible role of adipose tissue in mediating these changes. We first demonstrated that human and rat adipose tissue contain high levels of mRNA specific 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 gene-specific suppression of NPr-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 tissue obtained through subcutaneous peri-umbilical needle aspiration in obese and non-obese hypertensive patients. We found that NPr-A: NPr-C mRNA ratio was significantly lower in obese hypertensive patients as compared with non-obese hypertensives. These findings suggest that overxpression of the clearance receptor in the obese may trap more molecules of circulating ANP so reducing their biological activity at renal level. More recent results were obtained in obese hypertensive patients in whom the intravenous bolus injection 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 cGMP. The infusion of ANP after low-calorie diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis and natriuresis significantly increased only after caloric restriction and the effects of ANP infusion on BP were more pronounced. Taken together our 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 characteristic of obesity associated hypertension.
肥胖与高血压之间的关联众所周知，但体重相关变化对血压影响的病理生理学仍存在争议。尽管肥胖相关高血压被认为对钠敏感，但心房利钠肽（ANP）及其受体（NPr）系统可能的病理生理作用却很少受到关注。由于极低热量饮食或禁食诱导的体重减轻早期会伴随利尿和利钠显著增加以及循环ANP增加，我们将注意力集中在脂肪组织在介导这些变化中可能发挥的作用上。我们首先证明，人和大鼠脂肪组织中含有高水平的A 型（具有生物活性的NPr-A）和C 型（无生物活性的NPr-C）受体特异性mRNA。然后我们在大鼠中证明，禁食对脂肪组织中NPr-C基因表达具有组织特异性和基因特异性抑制作用，这似乎伴随着ANP生物活性增加。在对肥胖和非肥胖高血压患者通过皮下脐周针吸获取的脂肪组织中研究NPr-A和NPr-C基因表达的人体研究中，这些实验观察结果得到了证实。我们发现，与非肥胖高血压患者相比，肥胖高血压患者中NPr-A:NPr-C mRNA 比值显著更低。这些发现表明，肥胖者中清除受体的过度表达可能会捕获更多循环ANP分子，从而降低其在肾脏水平的生物活性。在肥胖高血压患者中获得了更新的结果，在极低热量饮食4天前后静脉推注ANP（0.6mg/kg体重），该饮食导致体重减轻，同时血压显著降低，尿中cGMP排泄增加。低热量饮食后输注ANP后，ANP水平升高，与饮食前观察到的情况相似，但血浆cGMP、利尿和利钠仅在热量限制后显著增加，且ANP输注对血压的影响更明显。综合我们的研究表明，脂肪组织中NPr-C的丰度可能在解释肥胖相关高血压至少部分钠潴留特征方面发挥重要作用。
