title: Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs.
abstract: Renal expression of the peptide hormone urotensin II (UII) and its receptor (UTR) are dependent on kidney maturation and anatomical regions. However, renal regional hemodynamic effects of UII in neonates are unclear. Here, we investigated regional hemodynamic responses to acute intrarenal arterial administration of UII in newborn pigs. Western immunoblotting and immunofluorescence confirmed UTR expression and membrane localization in newborn pig renal afferent arterioles and afferent arteriolar smooth muscle cells respectively. Intrarenal arterial bolus injections of human UII (hUII; 1-100  ng/kg) resulted in a dose-dependent decrease in total renal blood flow (RBF) and an increase in mean arterial pressure (MAP) and renal vascular resistance (RVR) in newborn pigs. Moreover, hUII dose dependently reduced cortical blood flow (CBF) but increased medullary blood flow (MBF) in the piglets. hUII-induced MAP elevation and hemodynamic changes were inhibited by urantide, a UTR antagonist, but not losartan, a type 1 angiotensin II receptor antagonist. U-73122, a phospholipase C (PLC) inhibitor, and 2-aminoethoxydiphenyl borate, an inositol 1,4,5 trisphosphate (IP₃) receptor antagonist, attenuated hUII-induced MAP and RVR elevations, RBF and CBF reductions, but not MBF increase. These findings indicate that intrarenal arterial administration of hUII elevates blood pressure and induces region-selective renal hemodynamic changes in newborn pigs. Our data also suggest that the PLC/IP₃ signaling pathway contributes to hUII-induced alterations in MAP, RBF, RVR, and CBF but not MBF in newborn pigs.
authors.affiliation: Department of Physiology, , University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Soni
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adebiyi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D062186:Arterial Pressure / Q000187:drug effects*; D001896:Boron Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*; D013552:Swine; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014579:Urotensins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001896:Boron Compounds; D004963:Estrenes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010446:Peptide Fragments; D011760:Pyrrolidinones; D014579:Urotensins; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C029677:urotensin II; C109986:2-aminoethoxydiphenyl borate; D010738:Type C Phospholipases; D019808:Losartan
keywords: Urotensin II; mean arterial pressure; neonates; renal arterioles; renal hemodynamics