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Atrial Natriuretic Peptide Alleviates Cardiovascular and Metabolic Disorders in a Rat Endotoxemia Model: A Possible Role for Its Anti-inflammatory Properties

Masaki Mori, Yoshitaka Yamanashi, Katsuya Kobayashi and Atsuhiro Sakamoto

Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School

Background: Atrial natriuretic peptide (ANP) plays important roles in the regulation of cardiovascular and renal homeostasis. Furthermore, several studies have shown that ANP may have anti-inflammatory activities. We hypothesized that ANP may alleviate cardiovascular and/or metabolic disorders in rats with lipopolysaccharide (LPS)-induced endotoxemia.
Methods: In rats anesthetized with pentobarbital, LPS was injected and ANP was continuously infused at 0.15 μg/kg/min. Mean arterial pressure and pulse rate were monitored hourly, and arterial blood gases were analyzed before LPS injection and at 1, 4, and 6 hours after LPS injection. The expression in the rat left ventricle of mRNAs encoding nitric oxide synthase 2 and 3 (iNOS, eNOS), heme oxygenase 1 and 2 (HO-1, 2), tumor necrosis factor α (TNFα), and interleukin (IL)-1β was measured with the real-time reverse transcriptase-polymerase chain reaction.
Results: LPS increased the expression of TNFα, IL-1β, iNOS, and HO-1, which was inhibited by infusion of ANP. Furthermore, the LPS-induced decrease in mean arterial pressure was attenuated, and the acid-base imbalance caused by increased lactate production was improved 6 hours after the administration of ANP.
Conclusions: Our results suggest that continuous infusion of ANP counteracts the cardiovascular and metabolic disorders associated with endotoxemia, possibly via anti-inflammatory mechanisms.

J Nippon Med Sch 2010; 77: 296-305

Keywords
atrial natriuretic peptide, lipopolysaccharide, tumor necrosis factor-α, nitric oxide synthase 2, real-time reverse transcriptase-polymerase chain reaction

Correspondence to
Masaki Mori, Department of Anesthesiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
nobunaga3@nms.ac.jp

Received, October 30, 2009
Accepted, September 9, 2010