Exogenous nitric oxide centrally enhances pulmonary reactivity in the normal and hypertensive rat

Daryl O Schwenke, James Todd Pearson, Hirotsugu Tsuchimochi, Hidezo Mori, Mikiyasu Shirai

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Abstract

1. 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 and reactivity. Centrally, NO inhibits sympathetic outflow, so we hypothesised that central NO would modulate pulmonary vascular tone and its reactivity to acute hypoxia, especially in the hypertensive state. 2. Male adult Sprague-Dawley rats were exposed to normoxia (N) or chronic hypoxia (CH; 12 O2) for 14 days. Mean pulmonary arterial pressure (MPAP), systemic mean arterial blood pressure (MABP), cardiac output and heart rate were then measured in pentobarbitone-anaesthetized, artificially ventilated rats. The N and CH rats were exposed to acute hypoxia (10 O2 for 4 min) after the intracerebroventricular (i.c.v.) administration of artificial cerebrospinal fluid (control) and then again after either i.c.v. NG-nitro-L-arginine methyl ester (L-NAME; 150 microg in 10 microL) or 3-morpholino-sydnonimine hydrochloride (SIN-1; 100 microg in 10 microL). 3. Chronic hypoxia caused pulmonary hypertension (MPAP 20+/-1 vs 30+/-1 mmHg in N and CH rats, respectively) and attenuated acute hypoxic pulmonary vasoconstriction (HPV). Central inhibition of NO synthesis (by l-NAME) did not alter baseline MPAP or the acute HPV in either N or CH rats, but it did elevate MABP. The NO donor SIN-1 did not alter baseline MPAP, but it did enhance (N rats) or restore (CH rats) the HPV and decreased MABP. 4. The results of the present study indicate that central NO has a limited role in the tonic modulation of MPAP during normoxia and after chronic hypoxia. However, the acute HPV seems to be enhanced by exogenous NO.
Original languageEnglish
Pages (from-to)952 - 959
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume32
Issue number11
Publication statusPublished - 2005

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