EFFECTS OF URODILATIN IN THE RAT-KIDNEY - COMPARISON WITH ANF AND INTERACTION WITH VASOACTIVE SUBSTANCES

We compared the effects of urodilatin (URO) and atrial natriuretic fac tor (ANF) in normal and hydronephrotic kidneys (HNK) of rats. Furtherm ore, the impact of blocking different vasoactive hormones on the actio n of natriuretic peptides on Vessels of cortical (C) and juxtamedullar y (JM) glomeruli was studied in HNK by using URO. In normal kidneys, e ffects of URO and ANF (1.2, 2.4, 4.8, 12, and 19 . 10(-11) mol . kg(-1 ) . min(-1) i.v.) were not significantly different. At 12 . 10(-11) mo l . kg(-1) . min(-1), URO and ANF increased urine flow 5.4 +/- 1.7 and 3.0 +/- 0.8-fold, increased urinary sodium excretion 20.7 +/- 8.8 and 10.3 +/- 4.0-fold, and decreased blood pressure by 13 +/- 2% and 12 /- 1%, respectively (mean +/- SEM). In HNK, URO and ANF (0.4, 0.9, and 2.0 . 10(-11) mol . kg(-1) . min(-1) i.v. and local application of 0. 5, 1.0, and 2.0 . 10(-9) M) dose-dependently dilated preglomerular ves sels (max approximate to 20%), constricted efferent arterioles (max ap proximate to 15%), and increased glomerular blood flow of C glomeruli in an identical fashion. Comparing URO effects on C and JM arterioles (0.4 and 0.9 . 10(-11) mol . kg(-1) . min(-1) i.v.), JM responses were about one third of C responses. Angiotensin converting enzyme inhibit ion (ACEI, 2 . 10(-6) mol . kg(-1) quinapril i.v.), combined ACEI and cyclooxygenase inhibition (CYOI, 2.8 . 10(-5) M indomethacin), and end othelin (ET) receptor blockade (10(-6) M BQ 123 and IRL 1038) diminish ed preglomerular vasodilation (C and JM) caused by URO infusion. Effer ent vasoconstriction (C and JM) caused by URO was exaggerated by block ade of nitric oxide synthesis (10(-5) M L-NAME and abolished by combin ed ACEI and CYOI, by bradykinin receptor blockade (4 . 10(-8) M Hoe 14 0), and by ET blockade. CYOI attenuated only JM efferent constriction. Our results show that URO and ANF possess equipotent vascular and sim ilar natriuretic effects in the rat kidney. The magnitude of preglomer ular vasodilation, which is directly mediated by these peptides, depen ds on the basal level of endogenous vasoconstrictors, while efferent v asoconstriction may be mediated by the secondary release of ET.