title: Effects of urodilatin in the rat kidney: comparison with ANF and interaction with vasoactive substances.
abstract: We compared the effects of urodilatin (URO) and atrial natriuretic factor (ANF) in normal and hydronephrotic kidneys (HNK) of rats. Furthermore, the impact of blocking different vasoactive hormones on the action of natriuretic peptides on vessels of cortical (C) and juxtamedullary (JM) glomeruli was studied in HNK by using URO. In normal kidneys, effects 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) mol.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-dependent dilated preglomerular vessels (max approximately 20%), constricted efferent arterioles (max approximately 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 inhibition (ACEI, 2.10(-6) mol.kg-1 quinapril i.v.), combined ACEI and cyclooxygenase inhibition (CYOI, 2.8.10(-5) M indomethacin), and endothelin (ET) receptor blockade (10(-6) M BQ 123 and IRL 1038) diminished preglomerular vasodilation (C and JM) caused by URO infusion. Efferent vasoconstriction (C and JM) caused by URO was exaggerated by blockade of nitric oxide synthesis (10(-5) M L-NAME) and abolished by combined ACEI and CYOI, by bradykinin receptor blockade (4.10(-8) M Hoe 140), and by ET blockade. CYOI attenuated only JM efferent constriction. Our results show that URO and ANF possess equipotent vascular and similar natriuretic effects in the rat kidney. The magnitude of preglomerular vasodilation, which is directly mediated by these peptides, depends on the basal level of endogenous vasoconstrictors, while efferent vasoconstriction may be mediated by the secondary release of ET.
authors.affiliation: Institute of Physiology, University of Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Endlich
authors.forename: W G
authors.initials: WG
authors.lastname: Forssmann
authors.forename: M
authors.initials: M
authors.lastname: Steinhausen
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004347:Drug Interactions; D065128:Endothelin Receptor Antagonists; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006869:Hydronephrosis / Q000378:metabolism; D007668:Kidney / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D065128:Endothelin Receptor Antagonists; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C056452:Ularitide; D009320:Atrial Natriuretic Factor