La glucosa en conjunto con péptidos derivados de cininógenos podrían actuar desde el aparato digestivo como bloqueadores de la acción diurética-natriurética del péptido natriurético auricular / Glucose in conjunction with peptides derived from kininogens might act from digestive tract as blockers of ANP mediated diuresis-natriuresis

This paper describes long term research efforts wich have lead: 1) to the identification of peptides present in pepsanurin, a peptidic fraction obtained by pepsin hydrolisis of plasma globulins that inhibits the renal excretory action of atrial natriuretic peptide (ANP) and 2) to the discovery of an unexpected role of glucose, as a requisite, for these inhibitory effects. The active peptides identified in pepsanurin are derived from plasma kininogens, substrates of the kallikrein-kinin system. Pro-kinins of 15, 16 and 18 aminoacids, and bradykinin itself, block ANP-induced diuresis and natriuresis when injected iv, ip or into, the duodenal lumen of anesthetized rats in picomol doses. Furthermore, a novel 20 aminoacids fragment derived from kininogen dominium-1, named PU-D1, is the most potent and longer lasting blocker of ANP renal effects. The anti-ANP effects of those peptides are prevented by B2- kinin receptor antagonists. The inhibition of ANP by kinins and PU-D1 was evident only in rats infused with isotonic glucose; whereas the excretory effect of ANP was not affected in fasted rats not infused, or infused with saline. These findings provide evidence that glucose facilitates liquid retention through a kinin-mediated inhibition of ANP excretory action that may be related to the prandial cycle

Hormonas vasodilatadoras en la insuficiencia cardíaca crónica: efecto de la inhibición de la enzima convertidora de angiotensina / Vasodilator hormones in chronic heart failure: effect of the inhibition of angiotensine converting enzyme

To evaluate the chronic effect of enalapril, in addition to digitalis and diuretics, in patients with chronic heart failure, nine patients with an idopathic dilated cardiomyopathy (8 males, aged 48 to 76 years old) under treatment with digitalis and diuretics, received enalapril 20 mg bid during eigth weeks. Before and after this treatment period resting left ventricular ejection fraction, functional class, plasma levels of atrial natriuretic factor and bradykinins (BK) and urinary excretion of kalikreins (BK) and prostaglandins E2 (PGE2) were measured. After enalapril therapy, there was a significant increase in maximal O2 consumption (14.8ñ1.2 to 18.6ñ1.5 ml/kg/min, p<0.05) and radionuclide LV ejection fraction (27.4ñ1.1 to 31.4ñ0.9 percent p<0.05). This was associated with a significant decrease in plasma ANP levels (559ñ158 to 178ñ54.8 pg/ml) and UK (391ñ112 to 243ñ92 Cu/24 h). The decrease in ANP levels, which is a well known marker of prognosis in CHF, could contribute to explain the sustained clinical benefits observed with ACE inhibitors in patients with CHF

El proceso digestivo y la regulación de la función excretora renal: pepsanuria y procininas inhibidoras de la acción diurética del péptido natriurético auricular / Digestive process and regulation of renal excretory function: pepsanurin and prokinin inhibitors of diuretic action of atrial natriuretic peptide

In order to clarify the blunting effect of peptides released by pepsin from blood plasma on ANP diuretic action, 2 prokinins designated PU-16 were tested. Both of them were able to inhibit in nanomolar doses the diuretic-saluretic action of 0.5 ug i.v. bolus of ANP given to anesthetized rats either by intravenous route or introduced in the duodenal lumen. PU-16 in doses of 0.5 ug and 1 ug were able to reduce in 72 and 96.5 per cent respectively the natriuresis induced bu 0.5 ug intravenous bolus of ANP. The data support the hypothesis that prokinins liberated in the digestive tract, could be physiological factors involved in hydrosaline homeostasis, moderating the ANP mediated increase of water, Na and K excretion during digestion

Pepsanurina en la insuficiencia cardíaca congestiva / Pepsanurin in congestive heart failure

We have identified a plasmatic substance, "pepsanurin" (PU) obtained by pepsin hydrolysis which inhibits the renal effects of the atrial natriuretic factor (ANF). To investigate whether patients with congestive heart failure (CHF) have increased plasma levels of PU we prepared PU from 10 patients with CHF class IV (NYHA), 9 patients with CHF class II or III and 16 healthy controls. Anesthetized rats were used to test the effects of ANF, 0.5 ug/100 g body weight i.v., before and following the intraperitoneal injection of 0.5 ml of PU. The inhibition of the diuretic and natriuretic effects of ANF was 40.9 ñ 11.9% and 49.8 ñ 12% respectively for control subjects. Corresponding figures for clas CHF patients were 62.3 ñ 3.1% and 73.8 ñ 3.5% (p < 0.02) and for class II-III patients 39.2 ñ 7.0% and 53.1 ñ 8.2% (NS). Accordingly, an increased capacity to generate PU may underlie the decreased sensitivity to ANF in patients with advanced CHF