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

Gozal, David, José E. Torres, Yair M. Gozal, andSanford M. Littwin. Effect of nitric oxide synthase inhibition on cardiorespiratory responses in the conscious rat. J. Appl. Physiol. 81(5): 2068-2077, 1996.Nitricoxide synthase (NOS) blockade was used to test the cardioventilatoryresponses to hypercapnia and hypoxia in freely behaving animals.Chronically instrumented adult Sprague-Dawley rats were studied beforeand after intravenous administration of either 100 mg/kg ofN^G-nitro-L-arginine methylester (L-NAME), a nonspecificNOS blocker, or 10 mg/kg ofS-methyl-L-thiocitrulline(SMTC), a selective neural NOS inhibitor.L-NAME injection inducedsustained blood pressure (BP) elevation with transient tachycardia andincreased minute ventilation (E), whichreturned to baseline within minutes. SMTC elicited similar, althoughtransient, BP increases; however, heart rate andE decreased.L-NAME and SMTC did not modifyoverall steady-state hypercapnic responses. In controlconditions, hypoxia induced early Eincreases with further E enhancementsat 30 min. L-NAME increased theearly E response to 10%O₂ but induced lateE reductions in hypoxia. SMTC did notchange early E responses but inducedmarked reductions in the later Ehypoxic responses. In control animals, hypoxia induced a significantheart rate increase. This increase was absent during the early response after SMTC and was followed in bothL-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 wasabsent after administration of NOS inhibitors. These findings suggestthat NOS activity exerts excitatory influences on respiration andcardiac chronotropy and sustained vasomotor tone during hypoxia. Wespeculate that NOS-mediated mechanisms may play an important role inhypoxia-induced ventilatory roll-off during wakefulness.