抄録
Chronic hypoxia causes sustained pulmonary hypertension and, although impairment of the pulmonary endothelial nitric oxide (NO) pathway has been implicated, no study has described the central role of NO in modulating pulmonary vascular tone or acute hypoxic pulmonary vasoconstriction (HPV). Centrally, NO inhibits sympathetic tone, so we hypothesised that acute central NO would modulate pulmonary vascular tone and acute HPV, especially in the hypertensive state. Male adult Sprague-Dawley rats were exposed to normoxia (N) or hypoxia (CH=12% O2) for 14 days. Mean pulmonary (MPAP) and systemic arterial pressure (MABP), cardiac output (CO) and heart rate (HR) were measured in anesthetized, artificially-ventilated rats. N- and CH-rats were exposed to acute hypoxia (10% O2 for 4 min) after the intracerebroventricular (icv) administration of aCSF (control) and again after either icv L-NAME (150μg in 10μl) or SIN-1 (100μg/10μl). Chronic hypoxia caused pulmonary hypertension (MPAP of 20±1 mmHg in N-rats, cf. 30±1 mmHg in CH-rats) and attenuated HPV. Central inhibition of NO synthesis (L-NAME) did not alter baseline MPAP or the acute HPV in either N-rats or CH-rats, but it did elevate MABP. The NO-donor (SIN-1) did not alter baseline MPAP, but it enhanced (N-rats) or restored (CH-rats) the HPV and decreased MABP. This study indicates that, although central NO has a limited role in the tonic modulation of MPAP, exogenous NO enhances the acute HPV. [Jpn J Physiol 55 Suppl:S87 (2005)]
