Kinins mediate the inhibition of atrial natriuretic peptide diuretic effect induced by pepsanurin

Pepsanurin is a peptidic fraction resulting from pepsin digestion of plasma globulins, that inhibits ANP renal excretory actions. We studied whether kinin-like peptides mediate the anti-ANP effect by testing if pepsanurin: 1) was blocked by the kinin B12 receptor antagonist HOE-140, 2) was produced from kininogen, and 3) was mimicked by bradykinin. Anti-ANP activity was assessed in anesthetized female rats by comparing the excretory response to two ANP boluses (0.5 mug iv) given before and after ip injection of test samples. Pepsanurin from human or rat plasma (1-5 mL/Kg), and bradykinin (5-20 mug/Kg), dose-relatedly inhibited ANP-induced water, sodium, potassium and cyclic GMP urinary excretion, without affecting arterial blood pressure. The same effect was exerted by pepsin hydrolysates of purified kininogen, whereas hydrolysates of kininogen-free plasma had no effect. HOE-140 (5 mug, iv) did not alter baseline, or ANP-induced excretion, but blocked the anti-ANP effects of pepsanurin. Histamine (15 mug/Kg) plus seroalbumin hydrolysates did not affect ANP response, despite inducing larger peritoneal fluid accumulation as compared with pepsanurin or bradykinin. We concluded that kinins cleaved from kininogen mediate the anti-ANP effects of pepsanurin by activation of kinin B2 receptors, independently of changes in systemic arterial pressure or peritoneal fluid sequestration.

Jorge Mardones: oration at this funeral service

Oration at the funeral service of Prof Jorge Mardones, M.D. A very successful and influential pharmacologist, he was Chairman of the Department of Pharmacology, Faculty of Medicine, University of Chile; President of the Academy of Sciences, Institute of Chile; National Prize of Sciences, 1977; and Minister of Public Health. He also served as Chief Editor of "Archivos de Biología y Medicina Experimentales" (former name of this journal) between 1964 and 1978.

Atrial natriuretic factors (ANF) and antidiuretic agents

Se demuesta que, en ratas anestesiadas y perfundidas con solución isotónica de glucosa, la administracíon i.v. previa de lisil-vasopresina, en dosis de 0.1 a 10 m, no inhibe la respuesta diurética y salurética del FNA (2.5 ug); en cambio, la dosis de 50 mU, que produce una elevación transitoria, pero acentuada de la presión arterial, intensifica el efecto del FNA. La pepsanurina obtenida de la hidrólisis de globulinas de 20 ml de plasma humano, administrada i.p., 40 a 60 m antes de la administración i.v. de FNA, produce una significativa inhibición de la respuesta diurética natriurética