Nitric oxide and angiotensin II regulation of renal hemodynamics in the developing piglet. 1996

M J Solhaug, and M R Wallace, and J P Granger
Department of Pediatrics, Eastern Virginia Medical School, Norfolk 23507, USA.

We have previously shown that nitric oxide (NO) is a more important intrarenal vasodilator in the developing animal compared with the adult. The interaction between NO and the renin angiotensin system in the developing kidney is not known. The purpose of this study was to determine the role of NO and angiotensin II in the regulation of developing renal function. We examined the effects of the inhibition of intrarenal NO synthesis with N-nitro-L-arginine methyl ester (L-NAME), 3 micro g/kg/min, intrarenally, administered after intrarenal infusion of either saline or an angiotensin II AT1 receptor antagonist [ATX (A-81988), 0.4 micro g/kg/min] in piglets, age 3 wk, and adult pigs. The developing piglet demonstrated significantly greater renal responses to L-NAME alone. Intrarenal NO synthesis inhibition after saline preinfusion decreased renal blood flow (RBF) in the piglet 29% compared with the adult pig 9%, but only in the piglet decreased GFR 31%, and increased plasma renin activity 57%. Intrarenal infusion of ATX significantly increased RBF in the piglet, 23%, although not altering RBF in the adult. The renal responses to L-NAME were significantly attenuated by ATX preinfusion in both age groups. After ATX pretreatment, L-NAME in piglets decreased RBF 14%, and abolished the change in GFR, whereas in adult pigs decreased RBF only 5%. CONCLUSIONS 1) angiotensin II may be a more important vasoconstrictor in the developing kidney and 2) NO is a more important regulator of renal function in the developing kidney through modulation of the renin angiotensin system.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D009539 Nicotinic Acids 2-, 3-, or 4-Pyridinecarboxylic acids. Pyridine derivatives substituted with a carboxy group at the 2-, 3-, or 4-position. The 3-carboxy derivative (NIACIN) is active as a vitamin. Acids, Nicotinic
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D012083 Renin A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19. Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D013777 Tetrazoles

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