Scholz H, Krämer B K, Hamann M, Götz K H, Kurtz A
Physiologisches Institut, Universität Regensburg, Germany.
Acta Physiol Scand. 1995 Oct;155(2):173-82. doi: 10.1111/j.1748-1716.1995.tb09962.x.
Using a preparation of isolated rat kidneys perfused at constant renal artery pressure (80 mmHG) we investigated the role of endothelins in the regulation of renin release. Addition of three related endothelins (ET-1, ET-2, ET-3) at a concentration of 10 pmol L(-1) tended to enhance renin secretion rates. Higher doses (100 pmol L(-1), 1 nmol L(-1)) of different ETs such as the selective ETB receptor agonist sarafotoxin S6c (100 pmol L(-1), 1 nmol L(-1)) inhibited renin release and increased renal vascular resistance with similar potency. These effects of ETs were blunted when calcium ions were removed from the perfusate. Renin release activated by isoproterenol (10 nmol L(-1)) was also significantly reduced with ET-1, -2 and -3 (1 nmol L(-1)). BQ-123 (500 nmol L(-1)), a selective ETA receptor antagonist, only attenuated, whilst the non-selective ET receptor blocker bosentan (Ro 47-0203, 10 micro mol L(-1)) almost abolished the renal vasopressor and renin inhibitory action of ET-1 and sarafotoxin S6c. BQ-123 and bosentan alone did not affect either perfusate flow or basal renin secretion rates in isolated perfused kidneys. These findings indicate that all three ET peptides equipotently inhibit renin secretion from the kidneys. Most of the vasopressor and renin inhibitory effect of ETs is mediated by ETB rather than ETA receptors involving a calcium-dependent signal transduction mechanism. Moreover, our results suggest that intrarenally released ETs do not contribute to the regulation of renin secretion from isolated perfused rat kidneys.
利用在恒定肾动脉压（80 mmHg）下灌注的离体大鼠肾脏制剂，我们研究了内皮素在肾素释放调节中的作用。添加浓度为10 pmol L⁻¹ 的三种相关内皮素（ET-1、ET-2、ET-3）倾向于提高肾素分泌率。不同内皮素的更高剂量（100 pmol L⁻¹、1 nmol L⁻¹），如选择性ETB受体激动剂沙拉新（100 pmol L⁻¹、1 nmol L⁻¹），以相似的效力抑制肾素释放并增加肾血管阻力。当从灌注液中去除钙离子时，内皮素的这些作用减弱。异丙肾上腺素（10 nmol L⁻¹）激活的肾素释放也被ET-1、-2和-3（1 nmol L⁻¹）显著降低。选择性ETA受体拮抗剂BQ-123（500 nmol L⁻¹）仅减弱了这种作用，而非选择性ET受体阻滞剂波生坦（Ro 47-0203，10 μmol L⁻¹）几乎消除了ET-1和沙拉新的肾血管升压和肾素抑制作用。单独使用BQ-123和波生坦对离体灌注肾脏的灌注液流量或基础肾素分泌率均无影响。这些发现表明，所有三种ET肽均能同等程度地抑制肾脏中的肾素分泌。内皮素的大多数血管升压和肾素抑制作用是由ETB而非ETA受体介导的，涉及钙依赖性信号转导机制。此外，我们的结果表明，肾内释放的内皮素对离体灌注大鼠肾脏中肾素分泌的调节没有作用。
