Abstract
Chronic global hypoxia causes sustained pulmonary hypertension of which an impairment of the pulmonary endothelial nitric oxide (NO) pathway has been implicated as a contributing factor. Within the CNS, NO also acts as a sympathoinhibitory substance, so that NO inhibition (e.g. using the NOS antagonist L-NAME) increases sympathetic outflow and ultimately arterial blood pressure. The effect of CNS NO inhibition on pulmonary vasculature is unknown. Thus, we hypothesised that the CNS NO may help modulate pulmonary vascular tone and act to attenuate the magnitude of pulmonary hypertension during chronic hypoxia. Male Sprague Dawley rats received a continuous intracerebroventricular infusion of either L-NAME (150 μg/kg/day) or vehicle (aCSF). Pulmonary arterial pressure (PAP) was measured in conscious rats using a pressure telemetric transmitter. One week after surgery, rats were exposed to chronic hypocapnic hypoxia (12% O2) for 2 weeks. As expected, chronic hypoxia significantly increased PAP. However, the central administration of L-NAME did not appear to alter the magnitude of the chronic hypoxia-induced pulmonary hypertension. These results suggest that the central inhibition of NO may not exacerbate the increase in sympathetic outflow and, thus, may not influence the pathomechanisms responsible for pulmonary hypertension during chronic hypoxia. In further experiments we will determine whether increasing central NO production (L-arginine infusion) attenuates the development of pulmonary hypertension during chronic hypoxia. [Jpn J Physiol 54 Suppl:S93 (2004)]
