AJP - Heart and Circulatory Physiology, Vol 272, Issue 2 843-H850, Copyright © 1997 by American Physiological Society

ARTICLES

Effects of inhibition of nitric oxide synthase by aminoguanidine in acute endotoxemia

C. E. Hock, K. Yin, G. Yue and P. Y. Wong
Department of Medicine, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford 08084, USA.

Nitric oxide (NO) has been implicated in the pathogenesis of the circulatory dysfunction of endotoxin shock. We investigated the effect of aminoguanidine (AG), an inhibitor of nitric oxide synthase (NOS) that is more selective for the inducible NOS, on the circulatory and inflammatory sequelae after administration of a bolus (10 mg/kg iv) of lipopolysaccharide (LPS) (Salmonella enteritidis). Rats receiving LPS + vehicle (LPS + Veh) exhibited a 73% decrease in mean arterial blood pressure (MABP) and a 50% decrease in cardiac index (CI) and SV index (SVI) within 10 min after LPS administration. MABP recovered to 64 +/- 3, 81 +/- 6, and 79 +/- 8 mmHg, at 60, 120, and 180 min post-LPS, respectively. However, CI and SVI remained depressed by 40-50% for the entire experimental period. Systemic vascular resistance (SVRI), heart rate (HR), and hematocrit were significantly elevated at 180 min after LPS administration. There was a 15-fold increase in plasma nitrite/nitrate and significantly elevated tissue nitrite/nitrate in the lung, heart, liver, and intestine after 3 h of acute endotoxemia. Treatment with AG markedly decreased plasma nitrite/nitrate but did not alter the initial hypotension or cardiac depression. However, at 60 min after LPS administration the HR, MABP, and SVRI were higher in the AG-treated rats compared with vehicle, whereas CI and SVI remained depressed. Myeloperoxidase activity was significantly increased in the lung but not in the other tissues after LPS. The AG infusion significantly reduced tissue nitrite/nitrate in the lung and heart compared with LPS + Veh. The data suggest that neither NO nor acute inflammatory cell accumulation is solely responsible for the depressed cardiovascular function after intravenous administration of LPS.

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