内肽酶-24.11抑制及心钠素清除受体配体对清醒大鼠对大鼠脑钠肽反应的影响。

Effect of endopeptidase-24.11 inhibition and of atrial natriuretic peptide clearance receptor ligand on the response to rat brain natriuretic peptide in the conscious rat.

Kirk J E, Wilkins M R

Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.

Br J Pharmacol. 1993 Sep;110(1):350-4. doi: 10.1111/j.1476-5381.1993.tb13816.x.

Abstract

The present studies examined the effect of (a) a specific endopeptidase-24.11 (E-24.11) inhibitor (candoxatrilat) and (b) a ligand for the atrial natriuretic peptide (ANP) clearance receptor (SC 46542) on the renal and blood pressure response to brain natriuretic peptide (BNP) in conscious rats. 2. Infusion of BNP 200 ng kg-1 min-1 for 60 min produced a small rise in urinary sodium and guanosine 3':5'-cyclic monophosphate (cyclic GMP) excretion with a non-significant fall in mean arterial blood pressure. 3. Candoxatrilat (3 mg kg-1) alone had no significant effect on sodium excretion or blood pressure but markedly potentiated the natriuretic response to BNP. 4. Similarly SC 46542 (68 micrograms kg-1; 6.8 micrograms kg-1 min-1) which produced no significant effect on its own, potentiated the natriuresis-induced by BNP, although the effect was of shorter duration compared to that of candoxatrilat. 5. The data indicate two approaches to the potentiation of the renal activity of BNP and suggest that BNP may mediate some of the activity of E-24.11 inhibitors reported in cardiac failure.

摘要

本研究检测了(a)一种特异性内肽酶-24.11（E-24.11）抑制剂（坎多沙坦酯）和(b)心房利钠肽（ANP）清除受体的配体（SC 46542）对清醒大鼠肾和血压对脑利钠肽（BNP）反应的影响。2. 以200 ng kg-1 min-1的剂量输注BNP 60分钟，可使尿钠和鸟苷3':5'-环磷酸（环磷酸鸟苷）排泄量略有增加，平均动脉血压有不显著下降。3. 单独使用坎多沙坦酯（3 mg kg-1）对钠排泄或血压无显著影响，但可显著增强对BNP的利钠反应。4. 同样，SC 46542（68微克 kg-1；6.8微克 kg-1 min-1）单独使用时无显著影响，但增强了BNP诱导的利钠作用，尽管其作用持续时间比坎多沙坦酯短。5. 数据表明了两种增强BNP肾脏活性的方法，并提示BNP可能介导了心力衰竭中报道的E-24.11抑制剂的某些活性。