RENAL EFFECTS OF NATRIURETIC PEPTIDE RECEPTOR BLOCKADE IN CIRRHOTIC RATS WITH ASCITES

The aim of this study was to assess the effect of HS-142-1, a recently discovered specific antagonist of endogenous natriuretic peptides, on systemic hemodynamics, renal function, and the renin-aldosterone syst em in rats with cirrhosis and ascites. The study consisted of three pr otocols, each including 10 conscious control rats and 10 conscious rat s with carbontetrachloride-induced cirrhosis with ascites. In protocol 1, HS-142-1 administration (by intravenous bolus of 20 mg.kg(-1). bod y weight in all protocols) was not associated with significant changes in mean arterial pressure, heart rate, cardiac output or total periph eral resistance in the two groups of animals. In protocol 2, HS-142-1 induced a significant reduction in glomerular filtration rate (from 4. 2 +/- 0.5 to 2.6 +/- 0.3 ml/min, p < 0.025) in control animals. A decr ease in renal plasma flow and an increase in renal vascular resistance also occurred, but these changes were not statistically significant. In cirrhotic rats, HS-142-1 resulted in a significant decrease in rena l plasma flow (from 10.9 +/- 0.7 to 4.3 +/- 0.6 ml/min, p < 0.001) and a significant increase in renal vascular resistance (from 6.0 +/- 0.6 to 16.3 +/- 2.7 mm Hg.min ml(-1), p < 0.025). Glomerular filtration r ate decreased more in cirrhotic rats with ascites than in control rats (from 3.8 +/- 0.3 to 1.3 +/- 0.2 ml/min, p < 0.001). Changes in urine how rate and urinary sodium excretion rate paralleled those of glomer ular filtration rate in both groups of animals. In protocol 3, HS-142- 1 administration was associated with a marked increase in plasma renin activity (from 17 +/- 3 to 39 +/- 9 ng.ml(-1).hr(-1), p < 0.01) and p lasma aldosterone concentration (from 130 +/- 12 to 268 +/- 48 pg.ml(- 1), p < 0.025) in cirrhotic rats with ascites. This association was no t observed in control animals (plasma renin activity from 1.6 +/- 0.3 to 1.6 +/- 0.5 ng.ml(-1).hr(-1), aldosterone from 45 +/- 15 to 44 +/- 16 pg.ml(-1)). These findings indicate that endogenous natriuretic pep tides play a critical role in the maintenance of renal function and in the regulation of the renin-aldosterone system in cirrhosis with asci tes. These peptides, however, are not critical to arterial pressure ho meostasis under the conditions studied.