Roles of atrial natriuretic factors in rats experimental models of hypertension, renal failure and heart failure

为探讨心钠素（ANF）在高血压、慢性肾功能衰竭和心力衰竭中的病理生理作用，本研究测定了高血压、慢性肾功能衰竭和慢性心力衰竭大鼠模型循环中ANF的水平，并观察了合成ANF对高血压、慢性肾功能衰竭和慢性心力衰竭的影响。我们还研究了合成的ANF对培养的大鼠血管平滑肌（VSM）、肾小球系膜（GM）和肾乳头状集合管（RPCT）细胞产生环GMP的影响，以阐明ANF的血管和肾脏作用机制。与对照组大鼠相比，在自发性高血压大鼠（SHR）和DOCA或醛固酮盐高血压大鼠中分别观察到循环心钠素水平升高。持续输注合成心钠素在降压剂量率衰减DOCA或醛固酮盐高血压，但不是在SHR的高血压。SHK或Wistar京都大鼠慢性肾功能衰竭残肾模型中循环心钠素水平也升高 ...更多信息 与对照动物相比，在通过结扎左冠状动脉诱导的慢性心力衰竭大鼠中，分别为ure和。在SHR肾消融术中，持续输注合成ANF可显著降低血压，改善肾功能损害。血管紧张素转换酶抑制剂也改善肾功能，这与循环ANF水平的降低有关。在慢性心力衰竭大鼠中，与对照大鼠相比，对分级剂量的合成ANF的利钠和利尿反应减弱。在体外研究中，合成ANF增加大鼠肾和肠系膜VSM，GM和RPCT培养细胞中的环GMP水平呈剂量依赖性。VSM和GM细胞对合成ANF的敏感性高于RPCT细胞，提示ANF可能通过其血管和肾脏作用在高血压、慢性肾功能衰竭和慢性心力衰竭的病理生理过程中发挥保护作用。少

To assess the pathophysiological roles of atrial natriuretic factor (ANF) in hypertension, renal failure and heart failure, we determined circulating levels of ANF and the effects of synthetic ANF in rats experimental model of hypertension, chronic renal failure or chronic heart failure. We also examined the effects of synthetic ANF on cyclic GMP production in rat cultured vascular smooth muscle (VSM), glomerular mesangium (GM) and renal papillary collecting tubule (RPCT) cells to elucidate the mechanisms of vascular and renal actions of ANF. Elevated levels of circulating ANF were observed in spontaneously hypertensive rats (SHR) and DOCA- or aldosterone-salt hypertensive rats compared to control rats, respectively. The sustained infusion of synthetic ANF at a rate of subdepressor dose attenuated the hypertension in DOCA- or aldosterone-salt hypertension, but not in SHR. Circulating levels of ANF were also elevated in SHK or Wistar Kyoto rats remnant kidney model of chronic renal fail … More ure and in rats with chronic heart failure, induced by ligation of left coronary artery compared to control animals, respectively. In SHR with renal ablation, the sustained infusion of synthetic ANF induced a significant reduction of blood pressure, and the impaired renal function ameliorated. Angiotensin converting enzyme inhibitors also ameliorated renal function, which was associated with the decrease in circulating levels of ANF. In rats with chronic heart failure, the responses of natriuresis and diuresis to graded dosed of synthetic ANF were attenuated compared to control rats. In vitro studies, synthetic ANF increased cyclic GMP levels dose-dependently in cultured cells from rat renal and mesenteric VSM, GM and RPCT. The sensitivity of VSM and GM cells to synthetic ANF were greater than that RPCT cells.These results suggest that ANF may play the protective roles in the pathophysioloqy of hypertension, chronic renal failure and chronic heart failure via its vascular and renal action. Less