Pulmonary vascular reactivity of spontaneously hypertensive rats is exacerbated in response to the central administration of exogenous nitric oxide

Abstract

1. Centrally, nitric oxide (NO) is a sympathoinhibitory substance. Spontaneously hypertensive rats (SHR) have an impaired central nitroxidergic system and, consequently, NO-mediated decrease in sympathetic activity is exacerbated in SHR compared with Wistar-Kyoto (WKY) rats. We have demonstrated previously that acute hypoxic pulmonary vasoconstriction (HPV) is enhanced by central NO administration. Therefore, in the present study, we hypothesized that accentuation of the HPV by NO would be exacerbated in SHR compared with WKY rats. 2. Mean pulmonary arterial pressure, systemic mean arterial blood pressure, cardiac output and heart rate were measured in pentobarbitone-anaesthetized, artificially ventilated, male SHR and WKY rats. The brief, transient response to a bolus intracerebroventricular (i.c.v.) dose of N(G)-nitro-L-arginine methyl ester (L-NAME; 150 microg in 10 microL) was recorded in all rats. Upon recovery, rats were exposed to acute hypoxia (10% O(2) for 4 min) before and after the i.c.v. administration of the NO donor 3-[4-morpholinyl]-sydnonimine-hydrochloride (SIN-1; 100 microg in 10 microL). 3. In WKY rats, central inhibition of NO synthesis by L-NAME caused a mild increase in tonic pulmonary vascular tone and induced a large systemic pressor response. These responses were not observed in SHR. In contrast, SIN-1 failed to alter tonic pulmonary vascular tone, although it enhanced the HPV in WKY rats and, significantly more so, in SHR. 4. These results confirm that accentuation of the HPV by NO is exacerbated in SHR compared with WKY rats. The mechanism(s) by which the HPV is accentuated by central NO remains to be fully elucidated, but is likely to be associated with the sympathoinhibitory effects of NO and, if so, supports the idea that the nitroxidergic system of the SHR is impaired. Further electrophysiological studies are essential to confirm these assumptions.