Effect of nitric oxide synthase inhibition on cardiorespiratory responses in the conscious rat

David Gozal, José E. Torres, Yair M. Gozal, and Sanford M. Littwin Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Departments of Pediatrics and Physiology, and Interdepartmental Neuroscience Program, Tulane University School of Medicine, New Orleans, Louisiana 70112 Received 29 November 1995; accepted in final form 11 June 1996. Gozal, David, José E. Torres, Yair M. Gozal, and Sanford M. Littwin. Effect of nitric oxide synthase inhibition on cardiorespiratory responses in the conscious rat. J. Appl. Physiol. 81(5): 2068-2077, 1996. Nitric oxide synthase (NOS) blockade was used to test the cardioventilatory responses to hypercapnia and hypoxia in freely behaving animals. Chronically instrumented adult Sprague-Dawley rats were studied before and after intravenous administration of either 100 mg/kg of N G -nitro- L -arginine methyl ester ( L -NAME), a nonspecific NOS blocker, or 10 mg/kg of S -methyl- L -thiocitrulline (SMTC), a selective neural NOS inhibitor. L -NAME injection induced sustained blood pressure (BP) elevation with transient tachycardia and increased minute ventilation ( E ), which returned to baseline within minutes. SMTC elicited similar, although transient, BP increases; however, heart rate and E decreased. L -NAME and SMTC did not modify overall steady-state hypercapnic responses. In control conditions, hypoxia induced early E increases with further E enhancements at 30 min. L -NAME increased the early E response to 10% O 2 but induced late E reductions in hypoxia. SMTC did not change early E responses but induced marked reductions in the later E hypoxic responses. In control animals, hypoxia induced a significant heart rate increase. This increase was absent during the early response after SMTC and was followed in both L -NAME- and SMTC-treated animals by significant heart rate reductions to values below room air. Similarly, the sustained BP response to hypoxia in control animals was absent after administration of NOS inhibitors. These findings suggest that NOS activity exerts excitatory influences on respiration and cardiac chronotropy and sustained vasomotor tone during hypoxia. We speculate that NOS-mediated mechanisms may play an important role in hypoxia-induced ventilatory roll-off during wakefulness. control of breathing; blood pressure; baroreceptor; chemoreceptor; whole body plethysmography; hypercapnia; hypoxia 0161-7567/96 $5.00 Copyright © 1996 the American Physiological Society