Pressor and renal regional hemodynamic effects of urotensin II in neonatal pigs

Abstract

Renal expression of urotensin II (UII) and its receptor (UTR) are dependent on kidney maturation and anatomical regions. However, renal regional hemodynamic effects of UII in neonates, in whom the kidneys are functionally immature, are unclear. Here, we investigated regional hemodynamic responses to acute intrarenal administration of UII in newborn pigs. Western immunoblotting and immunofluorescence indicated that UTR is expressed in newborn pig renal microvessels and microvascular smooth muscle cells. Intrarenal bolus injections of human UII (hUII; 1–100 ng·kg−1) 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. Cortical blood flow (CBF) measured by laser Doppler flowmetry was ~2‐fold higher than medullary blood flow (MBF) in newborn pigs. hUII dose‐dependently reduced CBF, but increased MBF in the pigs. hUII‐induced MAP elevation and hemodynamic changes were inhibited by urantide, a UTR inhibitor, but not losartan, a type 1 angiotensin II receptor inhibitor. U73122, a phospholipase C (PLC) inhibitor and 2‐aminoethoxydiphenyl borate, an inositol 1,4,5 trisphosphate (IP3) receptor blocker attenuated hUII‐induced MAP and RVR elevations, RBF and CBF reductions, but not MBF increase. These findings indicate that intrarenal administration of hUII elevates blood pressure and induces regional‐selective renal hemodynamic changes in newborn pigs. Our data also suggest that PLC/IP3 signaling pathway contributes to hUII‐induced alterations in MAP, RBF, RVR, and CBF, but not MBF in newborn pigs.