科研之友
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摘要
Moderate (approximately 2-fold) increases in plasma unconjugated bilirubin levels are able to attenuate the development of angiotensin II (Ang II)dependent hypertension. To determine the specific role of decreases in superoxide production to the blood pressurelowering effects of moderate hyperbilirubinemia (MHyB), we performed this study, in which the Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin was given to Ang IIinfused mice in the presence and absence of moderate hyperbilirubinemia. %26lt;br%26gt;Apocynin (14mM) was administered in the drinking water prior to treatment with UDP-glucuronosyltransferase 1A1 antisense morpholino (16 g/kg), which was administered by intravenous injection every third day. Treatments were started before the implantation of Ang IIcontaining minipumps (1g/kg/min) and continued throughout the protocol. %26lt;br%26gt;Ang II infusion increased blood pressure to 1452mm Hg. Apocynin treatment alone reduced blood pressure to 1355mm Hg, whereas MHyB alone decreased blood pressure to 1185mm Hg in Ang IIinfused mice. Prior inhibition of NADPH oxidase with apocynin did not result in a further decrease in blood pressure in MHyB mice, which averaged 1173mm Hg (n 6 mice per group). In aortic preparations, apocynin treatment decreased Ang IImediated superoxide production from 2433120 relative light units (RLU)/min/mg to 1851126 RLU/min/mg (n 4 mice per group), which was similar to levels observed in MHyB mice alone (1473132 RLU/min/mg) or in combination with apocynin (1503115 RLU/min/mg). %26lt;br%26gt;Our results indicate that MHyB lowers blood pressure by a mechanism that is partially dependent on the inhibition of superoxide production.
- 出版日期2013-7
