Dessì-Fulgheri P, Sarzani R, Serenelli M, Tamburrini P, Spagnolo D, Giantomassi L, Espinosa E, Rappelli A
Istituto di Medicina Clinica, Cattedra di Medicina Interna I, University of Ancona, Ancona, Italy.
Hypertension. 1999 Feb;33(2):658-62. doi: 10.1161/01.hyp.33.2.658.
The expression of the natriuretic peptide clearance receptor is abundant in human and rat adipose tissue, where it is specifically inhibited by fasting. In obese hypertensives, plasma atrial natriuretic peptide (ANP) levels were found to be lower than in obese normotensives. Therefore, the increased adipose mass might influence ANP levels and/or its biological activity. The aim of the present study was to evaluate whether the humoral, hemodynamic, and renal effects of exogenous ANP in obese hypertensives might be enhanced by a very low calorie diet. Eight obese hypertensives received a bolus injection of ANP (0.6 mg/kg) after 2 weeks of a normal calorie/normal sodium diet, and blood pressure (BP), heart rate, ANP, cGMP, plasma renin activity, and aldosterone were evaluated for 2 hours before and after the injection. Diuresis and natriuresis were measured every 30 minutes. The patients then started a low calorie/normal sodium diet (510 kcal/150 mmol/d) for 4 days, and then the ANP injection protocol was repeated. The low calorie diet induced a slight weight loss (from 90.6+/-1.1 to 87. 7+/-1.2 kg; P<0.01), which was accompanied by increase of cGMP excretion (from 146.0+/-10.1 to 154.5+/-9.5 nmol/24 h; P<0.05) together with a reduction of BP (P<0.01 versus basal levels). ANP injection after diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis, and natriuresis increased significantly only after diet. Similarly, the decrease of BP after ANP administration was significantly higher after diet (change in mean arterial pressure, -6.4+/-0.7 versus -4. 0+/-0.6 mm Hg; P<0.05) as well as that of aldosterone (P<0.01). These data show that a low calorie diet enhances the humoral, renal, and hemodynamic effects of ANP in obese hypertensives and confirm the importance of caloric intake in modulating the biological activity of ANP, suggesting that the natriuretic peptide system can play a role in the acute changes of natriuresis and diuresis associated with caloric restriction.
利钠肽清除受体在人和大鼠脂肪组织中表达丰富，禁食可特异性抑制其表达。在肥胖高血压患者中，发现血浆心房利钠肽（ANP）水平低于肥胖血压正常者。因此，增加的脂肪量可能会影响ANP水平和/或其生物活性。本研究的目的是评估极低热量饮食是否能增强外源性ANP对肥胖高血压患者的体液、血流动力学和肾脏效应。8名肥胖高血压患者在接受正常热量/正常钠饮食2周后，静脉注射一剂ANP（0.6 mg/kg），并在注射前后2小时评估血压（BP）、心率、ANP、环磷酸鸟苷（cGMP）、血浆肾素活性和醛固酮水平。每30分钟测量一次尿量和尿钠排泄量。然后患者开始低热量/正常钠饮食（510千卡/150毫摩尔/天），持续4天，之后重复ANP注射方案。低热量饮食导致体重略有下降（从90.6±1.1千克降至87.7±1.2千克；P<0.01），同时cGMP排泄量增加（从146.0±10.1纳摩尔/24小时增至154.5±9.5纳摩尔/24小时；P<0.05），血压降低（与基础水平相比，P<0.01）。饮食后注射ANP后，ANP水平升高幅度与饮食前相似，但血浆cGMP、尿量和尿钠排泄量仅在饮食后显著增加。同样，饮食后ANP给药后血压下降幅度显著更大（平均动脉压变化，-6.4±0.7与-4.0±0.6毫米汞柱；P<0.05），醛固酮下降幅度也更大（P<0.01）。这些数据表明，低热量饮食可增强外源性ANP对肥胖高血压患者的体液、肾脏和血流动力学效应，并证实热量摄入在调节ANP生物活性中的重要性，提示利钠肽系统可能在与热量限制相关的尿钠排泄和利尿的急性变化中发挥作用。
