Helwig J J, Musso M J, Judes C, Nickols G A
Laboratoire de Physiologie Renale Rene Leriche, Hospices Civils, Strasbourg, France.
Endocrinology. 1991 Sep;129(3):1233-42. doi: 10.1210/endo-129-3-1233.
The present study was designed to characterize the interaction of calcium and PTH in the control of renin release in isolated rat kidneys perfused in a closed circuit at constant flow. Kidneys were rendered nonfiltering using low perfusion pressures (70 mm Hg) and a hyperoncotic perfusate (100 g/liter BSA). Under these conditions, differences in perfusion pressure were less than 9 mm Hg between control and PTH-treated kidneys over the 50 min of perfusion. In the absence of PTH, renin release was inversely correlated with ionized calcium (Ca2+) concentration, with the highest release of renin noted with 1 mM EGTA and no added calcium. Also, verapamil treatment markedly elevated renin release, even in the presence of 2 mM Ca2+. In contrast, renin secretion was strongly depressed by 20 nM BAY-K8644 in the perfusate. In medium containing normal calcium concentrations (1 mM Ca2+), rat PTH(1-34) induced a 2-fold greater renin accumulation than in the control, non-PTH-treated kidneys. Isoproterenol induced a 5-fold stimulation under the same conditions. In the 0 Ca2+/1 mM EGTA perfusion, PTH did not elevate renin secretion. Renin release in response to PTH in 2 mM Ca2+ was similar to that observed in the 1 mM Ca2+ perfusion. PTH also reversed the effects of BAY-K8644 to suppress renin release. In verapamil-treated kidneys, PTH failed to stimulate renin release. These results indicate that PTH stimulates renin release by a process independent of the baroreceptors and macula densa. The Ca2+ modulation of PTH-induced renin release is consistent with the reported ability of PTH to block calcium channels and relax vascular smooth muscle.
本研究旨在描述在恒流闭路灌注的离体大鼠肾脏中，钙与甲状旁腺激素（PTH）在肾素释放控制中的相互作用。使用低灌注压力（70 mmHg）和高渗灌注液（100 g/升牛血清白蛋白）使肾脏失去滤过功能。在这些条件下，在50分钟的灌注过程中，对照肾脏和PTH处理的肾脏之间的灌注压力差异小于9 mmHg。在没有PTH的情况下，肾素释放与游离钙（Ca2+）浓度呈负相关，在添加1 mM乙二醇双四乙酸（EGTA）且未添加钙时肾素释放最高。此外，即使在存在2 mM Ca2+的情况下，维拉帕米处理也显著提高了肾素释放。相反，灌注液中20 nM的BAY-K8644强烈抑制了肾素分泌。在含有正常钙浓度（1 mM Ca2+）的培养基中，大鼠PTH（1-34）诱导的肾素积累比未处理的对照肾脏高2倍。在相同条件下，异丙肾上腺素诱导了5倍的刺激。在0 Ca2+/1 mM EGTA灌注中，PTH未提高肾素分泌。在2 mM Ca2+条件下，PTH刺激的肾素释放与在1 mM Ca2+灌注中观察到的相似。PTH还逆转了BAY-K8644抑制肾素释放的作用。在维拉帕米处理的肾脏中，PTH未能刺激肾素释放。这些结果表明，PTH通过独立于压力感受器和致密斑的过程刺激肾素释放。PTH诱导的肾素释放的Ca2+调节与报道的PTH阻断钙通道和舒张血管平滑肌的能力一致。
