Cardiopulmonary control in sleeping Sprague-Dawley rats treated with hydralazine

Abstract

To test the hypothesis that hydralazine can suppress spontaneous sleep-related central apnea, respiratory pattern, blood pressure, and heart period were monitored in Sprague-Dawley rats. In random order and on separate days, rats were recorded after intraperitoneal injection of 1) saline or 2) 2 mg/kg hydralazine. Normalized minute ventilation (NVI) declined significantly with transitions from wake to non-rapid-eye-movement (NREM) sleep (-5.1%; P = 0.01) and rapid-eye-movement (REM) sleep (-4.2%; P = 0.022). Hydralazine stimulated respiration (NVI increased by 21%; P < 0.03) and eliminated the effect of state on NVI. Blood pressure decreased by 17% after hydralazine, and the correlation between fluctuations in mean blood pressure and NVI changed from strongly positive during control recordings to weakly negative after hydralazine (P < 0.0001 for each). Postsigh and spontaneous apneas were reduced during NREM and REM sleep after hydralazine (P < 0.05 for each). This suppression was strongly correlated with the reduction in blood pressure and with the degree of respiratory stimulation. We conclude that mild hydralazine-induced hypotension leads to respiratory stimulation and apnea suppression.