Nomega-nitro-L-arginine methyl ester (L-NAME) amplifies the pulmonary hypertensive response to microparticle injections in broilers

Department of Poultry Science, University of Arkansas, Fayetteville, Arkansas 72701, USA. rwideman@uark.edu

We tested the hypothesis that microparticles entrapped within the pulmonary vasculature elicit the production of nitric oxide (NO) in quantities sufficient to modulate the combined impact of physical occlusion plus contemporaneously released vasoconstrictors. In experiment 1, male broilers were given an injection of the NO synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME), followed by an intravenous injection of cellulose microparticles while the pulmonary arterial pressure (PAP) and cardiac output (CO) were recorded. When L-NAME was used to block NO synthesis induced by the microparticles, an early peak of pulmonary hypertension was revealed that rarely developed in the absence of L-NAME. The subsequent more prolonged increases in PAP and pulmonary vascular resistance (PVR) were greater in amplitude and duration in broilers pretreated with L-NAME than in broilers in the control group. These amplified responses occurred in spite of a simultaneous reduction in CO, thereby conclusively demonstrating that inhibiting NOS permitted the development of a much more profound increase in the PVR. In experiment 2 the mortality triggered within 48 h after injecting microparticles was evaluated in the presence and absence of L-NAME. The 48 h postinjection mortality more than doubled when L-NAME was combined with microparticle injection doses that otherwise caused relatively low mortality in the absence of L-NAME. Experiment 3 was conducted to determine whether NO contributes to the systemic hypoxemia that develops after microparticles are injected. L-NAME administration had no impact on the magnitude and duration of the microparticle induced decline in the percentage saturation of hemoglobin with oxygen (%HbO2). Evidently hypoxemia per se contributes relatively little to the amplified pulmonary vasoconstriction and 48 h postinjection mortality triggered by microparticle injections in broilers pretreated with L-NAME. These observations indicate that NO modulates the responses to vasoconstrictors released when microparticles become entrapped in the pulmonary vasculature. Inhibition of NOS by L-NAME exposed a more dramatic increase in PVR and pulmonary hypertension leading to enhanced mortality in response to microparticle injections.

This article has been cited by other articles:

				R. F. Wideman, O. T. Bowen, and G. F. Erf Broiler pulmonary hypertensive responses during lipopolysaccharide-induced tolerance and cyclooxygenase inhibition Poult. Sci., January 1, 2009; 88(1): 72 - 85. [Abstract] [Full Text] [PDF]

				K. R. Hamal, R. Wideman, N. Anthony, and G. F. Erf Expression of Inducible Nitric Oxide Synthase in Lungs of Broiler Chickens Following Intravenous Cellulose Microparticle Injection Poult. Sci., April 1, 2008; 87(4): 636 - 644. [Abstract] [Full Text] [PDF]

				M. E. Chapman, R. L. Taylor, and R F. Wideman Jr. Analysis of Plasma Serotonin Levels and Hemodynamic Responses Following Chronic Serotonin Infusion in Broilers Challenged with Bacterial Lipopolysaccharide and Microparticles Poult. Sci., January 1, 2008; 87(1): 116 - 124. [Abstract] [Full Text] [PDF]

				A. G. Lorenzoni, N. B. Anthony, and R. F. Wideman Jr. Transpulmonary Pressure Gradient Verifies Pulmonary Hypertension is Initiated by Increased Arterial Resistance in Broilers Poult. Sci., January 1, 2008; 87(1): 125 - 132. [Abstract] [Full Text] [PDF]

				S. Stebel and R. F. Wideman Pulmonary Hemodynamic Responses to Intravenous Prostaglandin E2 in Broiler Chickens Poult. Sci., January 1, 2008; 87(1): 138 - 145. [Abstract] [Full Text] [PDF]

				A. G. Lorenzoni and R. F. Wideman Jr. Inhaling One Hundred Percent Oxygen Eliminates the Systemic Arterial Hypoxemic Response of Broilers to Intravenous Microparticle Injections Poult. Sci., January 1, 2008; 87(1): 146 - 154. [Abstract] [Full Text] [PDF]

				O. T. Bowen, G. F. Erf, M. E. Chapman, and R. F. Wideman Jr. Plasma Nitric Oxide Concentrations in Broilers After Intravenous Injections of Lipopolysaccharide or Microparticles Poult. Sci., December 1, 2007; 86(12): 2550 - 2554. [Abstract] [Full Text] [PDF]

				R. F. Wideman, M. E. Chapman, K. R. Hamal, O. T. Bowen, A. G. Lorenzoni, G. F. Erf, and N. B. Anthony An Inadequate Pulmonary Vascular Capacity and Susceptibility to Pulmonary Arterial Hypertension in Broilers Poult. Sci., May 1, 2007; 86(5): 984 - 998. [Abstract] [Full Text] [PDF]

				M. E. Chapman and R. F. Wideman Jr. Evaluation of the Serotonin Receptor Blocker Methiothepin in Broilers Injected Intravenously with Lipopolysaccharide and Microparticles Poult. Sci., December 1, 2006; 85(12): 2222 - 2230. [Abstract] [Full Text] [PDF]

				O. T. Bowen, R. F. Wideman, N. B. Anthony, and G. F. Erf Variation in the Pulmonary Hypertensive Responsiveness of Broilers to Lipopolysaccharide and Innate Variation in Nitric Oxide Production by Mononuclear Cells Poult. Sci., August 1, 2006; 85(8): 1349 - 1363. [Abstract] [Full Text] [PDF]