Effects of angiotensin II and the AT(1) receptor antagonist losartan on the renal excretion of urodilatin

Background: The precise mechanisms regulating the natriuretic peptide urodi latin (ANP-95-126) remain to be defined, Renal excretion of urodilatin (UUR OV) has been shown to be modified by variations in plasma sodium and renal perfusion pressure. This suggests a relationship between urodilatin and the renin-angiotensin system, Methods: We investigated the effects of angioten sin II (All, 0.1 nmol/l) and the AT(1) receptor antagonist losar-tan (LS, 1 mu mol/l) on UUROV and renal function in isolated rat kidneys perfused for 180 min in a closed circuit system. A further series employing a vasoconst ricting concentration of endothelin-l (ET-1, 0.01 nmol/l) was performed to explore the effects of vasoconstriction and glomerular filtration rate (GFR ) on UUROV. Results: Urine flow (UV) and urinary sodium excretion (UN,V) de creased and renal vascular resistance (PVP) increased after treatment with All (n = 5) in comparison with a control group (n = 6; p < 0.05). Treatment with LS (0 = 5) and All+LS (0 = 5) had no significant effect on these para meters. GFR decreased after All (p < 0.05) and was not significantly altere d by other interventions. UUROV decreased after All (p < 0.05) and was comp arable to the control group after LS and All+LS. ET-1 (n = 5) induced a sig nificant increase in RVR and decreased UV and UN,V (p ( 0.05). Point-to-poi nt analysis revealed that the ET-1-induced vasoconstriction and the subsequ ent decrease in GFR had no effect on UUROV Conclusions: This suggests that vasoconstrictory concentrations of All decrease UUROV in the isolated perfu sed rat kidney. The lack of effect of ET-1 on UUROV suggests that the All-i nduced alterations in urodilatin excretion cannot be explained by vasoconst riction per se, Copyright (C) 2001 S.Karger AG, Basel.