Franco-Saenz R, Atarashi K, Takagi M, Takagi M, Mulrow P J
Department of Medicine, Medical College of Ohio, Toledo 43699.
J Cardiovasc Pharmacol. 1989;13 Suppl 6:S31-5.
Atrial natriuretic factor (ANF) inhibits basal and stimulated aldosterone production in vitro and in vivo. Infusions of ANF have been reported to inhibit renin release in several species, including humans. A 4-h infusion of ANF into 12 patients with mild hypertension reduced plasma aldosterone at 2 and 4 h, with a rebound increase 2 h after the end of the infusion. Plasma renin activity also showed a mild but significant reduction at 2 h with a rebound increase at 6 h. The effect of ANF on renin release in vitro is controversial. Using a superfusion system of rat renal cortical slices and of dispersed juxtaglomerular (JG) cells, we found that ANF did not affect basal or isoproterenol-stimulated renin release by the kidney slices or dispersed JG cells. These studies suggest that ANF does not inhibit renin release by a direct effect on the JG cells and that the inhibition of renin release found in vivo studies may be mediated through a macula densa mechanism. Since calcium plays an important role in aldosterone secretion, we investigated the effect of ANF on calcium fluxes in rat adrenal glomerulosa cells. ANF did not affect either calcium influx or calcium efflux in rat adrenal glomerulosa cells. These studies suggest that the inhibitory effect of ANF on aldosterone production is distal to the calcium messenger system.
心房利钠因子(ANF)在体外和体内均可抑制基础状态及刺激状态下的醛固酮生成。据报道,在包括人类在内的多个物种中,输注ANF可抑制肾素释放。对12例轻度高血压患者输注ANF 4小时后,2小时和4小时时血浆醛固酮水平降低,输注结束后2小时出现反跳性升高。血浆肾素活性在2小时时也出现轻度但显著降低,6小时时出现反跳性升高。ANF对体外肾素释放的影响存在争议。利用大鼠肾皮质切片和分散的肾小球旁(JG)细胞的灌注系统,我们发现ANF对肾切片或分散的JG细胞的基础状态或异丙肾上腺素刺激的肾素释放均无影响。这些研究表明,ANF并非通过直接作用于JG细胞来抑制肾素释放,体内研究中发现的肾素释放抑制可能是通过致密斑机制介导的。由于钙在醛固酮分泌中起重要作用,我们研究了ANF对大鼠肾上腺球状带细胞钙通量的影响。ANF对大鼠肾上腺球状带细胞的钙内流或钙外流均无影响。这些研究表明,ANF对醛固酮生成的抑制作用发生在钙信使系统的下游。