ANGIOTENSIN II AND BRADYKININ BLOCKADE ON RENAL FUNCTION AND HEART FAILURE

充血性心力衰竭（CHF）的特征是心脏功能下降， 输出（C.O）。CO的减少激活了一系列复杂的， 增加钠潴留的多因素代偿反应， 导致水肿形成。虽然，肾素血管紧张素系统似乎 为了在这方面发挥关键作用， 答案并不完全清楚。 我们研究了：1）心钠素对肾脏的影响 （ANP 8 -33）通过创建一个 慢性治疗对大鼠下腔静脉瘘（ACF）的影响 氯沙坦，一种血管紧张素AT-1受体拮抗剂， 心钠素在失代偿性心力衰竭大鼠中的排泄和肾脏对心钠素的反应; 和3）缓激肽B2受体拮抗剂HOE-140对 心钠素对代偿性心力衰竭大鼠肾脏的影响。 在对照组，ANP（10- 50 μ g/kg/h）剂量依赖性增加 尿流率（UV）、绝对钠排泄量（UNaV）和尿 cGMP排泄（UcGMPV）。将相同剂量的ANP注入大鼠体内 代偿性CHF引起显著的钠尿、利尿和 UcGMPV增加，而在失代偿性CHF大鼠中， UcGMPV反应明显减弱。长期氯沙坦治疗， 在失代偿大鼠中导致显著的尿钠排泄，但在 补偿和对照大鼠。此外，氯沙坦治疗恢复了 失代偿大鼠对ANP的利钠和UcGMPV反应。 用HOE-140（100 nmol/kg/h）处理代偿大鼠， 影响其肾脏对ANP的反应。此外，输注HOE-140 单独进入代偿大鼠对他们的基础UV没有显着影响 或UNAV。 这些发现表明：1）血管紧张素II在血管紧张素受体的形成中起主要作用。 钠潴留的发展和对ANP的肾反应迟钝 提示氯沙坦是治疗心源性水肿良好药物， 2)缓激肽剂量不调节内源性急性肾反应 或外源性心钠素。

Congestive heart failure (CHF) is characterized by a reduction in cardiac output (C.O). The reduction in C.O activates a series of complex and multifactorial compensatory responses that increase sodium retention and lead to edema formation. Although, the renin angiotensin system appears to play a key role in this regard, the mechanisms underlying these responses are not fully known. We investigated 1) The renal effects of atrial natriuretic peptide (ANP8-33) before and after the induction of CHF by creation of an aortocaval fistula (ACF) in rats; 2) The effects of chronic treatment with losartan, an angiotensin AT-1 receptor antagonist, on sodium excretion and the renal response to ANP in rats with decompensated CHF; and 3) The effects of HOE-140, a bradykinin B2 receptor antagonist, on the renal response to ANP in rats with compensated CHF. In control rats, ANP (10-50microg/kg/h) caused dose dependent increases in urine flow (UV), absolute sodium excretion (UNaV) and urinary excretion of cGMP (UcGMPV). Infusion of the same doses of ANP into rats with compensated CHF induced remarkable natriuresis, diuresis and an increase in UcGMPV, whereas in rats with decompensated CHF the renal responses UcGMPV were markedly blunted. Chronic losartan treatment, resulted in dramatic natriuresis in decompensated rats, but not in compensated and control rats. Furthermore, losartan treatment restored the natriuretic and UcGMPV responses of decompensated rats to ANP. Treatment of the compensated rats with HOE-140 (100 nmol/kg/h) did not affect their renal response to ANP. In addition, infusion of HOE-140 alone into compensated rats had no significant effect on their basal UV or UNaV. These findings indicate that: 1) angiotensin II plays a major role in the development of sodium retention and in the blunted renal response to ANP in CHF and suggest that losartan is good therapy for cardiac edema, and 2) bradykinin dose not modulate the acute renal response to endogenous or exogenous ANP in compensated CHF.