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Am J Hypertens. 2013 Jul;26(7):918-23. doi: 10.1093/ajh/hpt038. Epub 2013 Mar 12.

Antihypertensive actions of moderate hyperbilirubinemia: role of superoxide inhibition.

Author information

1
Department of Physiology & Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi, USA. dstec@umc.edu

Abstract

BACKGROUND:

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 pressure-lowering effects of moderate hyperbilirubinemia (MHyB), we performed this study, in which the Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin was given to Ang II-infused mice in the presence and absence of moderate hyperbilirubinemia.

METHODS:

Apocynin (14mM) was administered in the drinking water prior to treatment with UDP-glucuronosyltransferase 1A1 antisense morpholino (16 μg/kg), which was administered by intravenous injection every third day. Treatments were started before the implantation of Ang II-containing minipumps (1μg/kg/min) and continued throughout the protocol.

RESULTS:

Ang II infusion increased blood pressure to 145±2mm Hg. Apocynin treatment alone reduced blood pressure to 135±5mm Hg, whereas MHyB alone decreased blood pressure to 118±5mm Hg in Ang II-infused mice. Prior inhibition of NADPH oxidase with apocynin did not result in a further decrease in blood pressure in MHyB mice, which averaged 117±3mm Hg (n = 6 mice per group). In aortic preparations, apocynin treatment decreased Ang II-mediated superoxide production from 2433±120 relative light units (RLU)/min/mg to 1851±126 RLU/min/mg (n = 4 mice per group), which was similar to levels observed in MHyB mice alone (1473±132 RLU/min/mg) or in combination with apocynin (1503±115 RLU/min/mg).

CONCLUSIONS:

Our results indicate that MHyB lowers blood pressure by a mechanism that is partially dependent on the inhibition of superoxide production.

KEYWORDS:

NADPH oxidase; angiotensin II; bilirubin; blood pressure; heme oxygenase; hypertension

PMID:
23482378
PMCID:
PMC3731819
DOI:
10.1093/ajh/hpt038
[Indexed for MEDLINE]
Free PMC Article
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