ABSTRACT
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
Subject(s)
Animals , Rats , Digestion/physiology , Digestive System , Diuresis/drug effects , Natriuresis/physiology , Atrial Natriuretic Factor/antagonists & inhibitors , Peptides/urine , Atrial Natriuretic Factor/pharmacokineticsABSTRACT
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