Herrmann H C, Dzau V J
Circ Res. 1983 Mar;52(3):328-34. doi: 10.1161/01.res.52.3.328.
The in vivo generation of angiotensin appears to be dependent on both plasma renin and angiotensinogen concentrations. Much less is known about the control of hepatic angiotensinogen synthesis and release, as compared to that of renin. In this study, we examined the feedback regulation of angiotensinogen synthesis and release by various components of the renin-angiotensin system, using an in vitro rat liver slice system. Livers were removed for study from rats which were subjected to various systemic infusions or physiological perturbations. Infusion of angiotensin II has been reported to increase angiotensinogen release rate. However, infusion of angiotensin I (with simultaneous suppression of plasma renin by antirenin antibody infusion and angiotensin II production by captopril administration) had no effect on the angiotensinogen release rate. Direct infusion of renin in rats treated with captopril resulted in further suppression of the angiotensinogen release rate, compared with those given captopril alone. We postulate that renin (or des-angiotensin I-angiotensinogen) inhibits the angiotensinogen release rate, whereas angiotensin II stimulates it. Angiotensin I has no effect on angiotensinogen release rate. This hypothesis was evaluated further in rats with various physiological states. Indeed, when conditions were such that the renin-angiotensin system was completely suppressed, such as binephrectomy and antirenin antibody infusion, angiotensinogen release rate was markedly stimulated. When angiotensin II production was prevented by captopril treatment, angiotensinogen release rate declined. This appeared to be the case for all states of sodium balance. Thus, angiotensinogen release rate is subject to a complex feedback control by other components of the renin-angiotensin system.
血管紧张素在体内的生成似乎取决于血浆肾素和血管紧张素原的浓度。与肾素相比，人们对肝脏血管紧张素原合成和释放的调控了解较少。在本研究中，我们使用体外大鼠肝切片系统，研究了肾素-血管紧张素系统各组分对血管紧张素原合成和释放的反馈调节。从接受各种全身输注或生理扰动的大鼠身上取出肝脏进行研究。据报道，输注血管紧张素II可增加血管紧张素原释放速率。然而，输注血管紧张素I（同时通过输注抗肾素抗体抑制血浆肾素，并通过给予卡托普利抑制血管紧张素II生成）对血管紧张素原释放速率没有影响。与单独给予卡托普利的大鼠相比，在给予卡托普利的大鼠中直接输注肾素导致血管紧张素原释放速率进一步受到抑制。我们推测肾素（或脱血管紧张素I-血管紧张素原）抑制血管紧张素原释放速率，而血管紧张素II则刺激其释放。血管紧张素I对血管紧张素原释放速率没有影响。在处于各种生理状态的大鼠中进一步评估了这一假设。事实上，当肾素-血管紧张素系统被完全抑制时，如双侧肾切除和输注抗肾素抗体，血管紧张素原释放速率会受到明显刺激。当通过卡托普利治疗阻止血管紧张素II生成时，血管紧张素原释放速率下降。在所有钠平衡状态下似乎都是如此。因此，血管紧张素原释放速率受到肾素-血管紧张素系统其他组分的复杂反馈控制。
