The Beneficial Effect of Atrial Natriuretic Peptide on Cyclosporine Nephrotoxicity

Abstract

Nephrotoxicity is the most common and important side effect of cyclosporine (CyA) therapy. It is characterized by a fall in glomerular filtration rate (GFR) and by a decrease in sodium and water excretion. Since atrial natriuretic peptide (ANP) has been shown to increase GFR and to cause a potent diuretic and natriuretic effect, we have investigated the potential beneficial action of ANP on CyA induced renal injury. To this end two groups of animals were studied: 1) rats that received an intravenous infusion of CyA (20 mg/kg body weight) (acute studies) and 2) rats that have been treated with daily intraperitoneal injections of CyA (20 mg/kg body weight) for a total of seven days (chronic studies). To both groups of rats synthetic ANP was administered intravenously as a bolus (10 micrograms/kg) and then as a constant infusion (1 microgram/kg/min). In group 1 the CyA administration resulted in a decrease in GFR, urine output, urinary sodium and potassium excretion. After ANP infusion there was a prompt restoration of GFR, with a large rise in urine, sodium and potassium excretion rates. Similar effects on renal hemodynamics and electrolyte excretion rates were detected after ANP administration in chronic CyA treatment. These data show that the administration of ANP to rats that have been exposed to acute or chronic CyA treatment is able to reverse the harmful effect of CyA on renal function.