title: Protective effect of perindoprilat in the hypoxemia-induced renal dysfunction in the newborn rabbit.
abstract: The renal effects of acute hypoxemia and the ability of perindoprilat, a potent angiotensin-converting enzyme inhibitor, to prevent these effects were assessed in 31 anesthetized and mechanically ventilated newborn (5 to 8 d of age) rabbits. Renal blood flow (RBF) and GFR were determined by the clearances of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In eight normoxemic rabbits (group 1), the i.v. infusion of saline did not change renal and hemodynamic functions. In eight additional rabbits, acute hypoxemia (PaO2= 40 mm Hg) induced a significant decrease in mean blood pressure (-8+/-2%), RBF (-36+/-3%), and GFR (-31+/-3%) and an increase in renal vascular resistance (+50+/-12%). A third group of newborn animals (n=7) was used to determine the renal effects of perindoprilat administration (20 microg/kg) under normoxemic conditions. RBF significantly increased (+15+/-2%) and renal vascular resistance significantly decreased (-15+/-3%), whereas GFR, mean blood pressure, and filtration fraction did not change significantly. In group 4 (n=7), perindoprilat infusion completely prevented the hypoxemia-induced alterations in GFR and renal vascular resistance and partially prevented the fall in RBF. These results demonstrate that angiotensin II modulates the renal immature microcirculation and that inhibition of its formation effectively prevents the hypoxemia-induced decrease in GFR.
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Huet
authors.forename: D S
authors.initials: DS
authors.lastname: Semama
authors.forename: J B
authors.initials: JB
authors.lastname: Gouyon
authors.forename: J P
authors.initials: JP
authors.lastname: Guignard
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000378:metabolism; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007211:Indoles / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011817:Rabbits
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C053500:perindoprilat; D001920:Bradykinin