Lazúrová I, Kramer H J
II. interná klinika FN Kosice.
Vnitr Lek. 1994 Mar;40(3):194-8.
Due to its physiological and pharmacological action ANF could be an ideal diuretic and vasorelaxation product in the treatment of oedema and essential hypertension. Experimental and clinical investigations in oedematous conditions revealed a very slight diuretic and natriuretic effect of ANF, as compared with healthy subjects. This is due to the reduced renal perfusion pressure, the increased RAAS activity, enzymatic degradation of ANF by endopeptidase and also its inactivation via C-receptors. Moreover the use of ANF is very limited due to its short half-life and peptide structure. In recent years therefore new possibilities are sought how to influence the metabolism of endogenous ANF and thus increase its activity. Neutral endopeptidase inhibitors (NEP) inhibit ANF degradation, increase thus its plasma level and in cardiac weakntlakess have a marked diuretic and natriuretic effect. The administration of NEP inhibitors in patients with essential hypertension did not reveal so far an adequate effect on blood pressure. Inhibitors of C-receptors potentiate also the effect of endogenous ANF. In experiments they enhance Na excretion and lead to a drop of blood pressure. Recently another natriuretic peptide was detected--urodilatine. In experimental and clinical studies in cardiac failure urodilatine administration leads to an increase of diuresis and natriuresis greater than after ANF. Haemodynamic effects after urodilatine are also greater than after ANF whereby urodilatine does not cause reflex tachycardia and is resistant to peptidase degradation. Its therapeutic administration is a new perspective in the treatment of oedematous conditions and essential hypertension.
由于其生理和药理作用,心房钠尿肽可能是治疗水肿和原发性高血压的理想利尿剂和血管舒张剂。在水肿状态下的实验和临床研究表明,与健康受试者相比,心房钠尿肽的利尿和排钠作用非常轻微。这是由于肾灌注压降低、肾素 - 血管紧张素 - 醛固酮系统(RAAS)活性增加、内肽酶对心房钠尿肽的酶促降解以及其通过C受体的失活。此外,由于心房钠尿肽半衰期短和肽结构的原因,其应用非常有限。因此,近年来人们一直在寻找新的方法来影响内源性心房钠尿肽的代谢,从而增加其活性。中性内肽酶抑制剂(NEP)可抑制心房钠尿肽的降解,从而提高其血浆水平,在心力衰竭患者中具有显著的利尿和排钠作用。迄今为止,在原发性高血压患者中使用NEP抑制剂对血压并未显示出足够的效果。C受体抑制剂也可增强内源性心房钠尿肽的作用。在实验中,它们可增加钠排泄并导致血压下降。最近发现了另一种利钠肽——尿舒张素。在心力衰竭的实验和临床研究中,给予尿舒张素导致的利尿和利钠作用比给予心房钠尿肽后更大。尿舒张素后的血流动力学效应也比心房钠尿肽后的更大,而且尿舒张素不会引起反射性心动过速,并且对肽酶降解具有抗性。其治疗应用是治疗水肿状态和原发性高血压的一个新的前景。