Ventilatory responses of the rat to mild hypercapnic stimulation before and after almitrine bismesylate

In pentobarbital-anesthetized rats, hyperventilatory responses to rectangular mild hypercapnic normoxic gas mixtures inhalation were analysed. Hyperventilation dynamics were characterized by a logarithmic curve whose delay (T0) and half response time (T50-T0) were calculated. These values were established in nervously intact (IR), vagotomized (XT), surgically chemodenervated (CDN) rats and in IR-rats after almitrine bismesylate (ALM) pretreatment. In IR and XT-rats, T0 and T50 - T0 were larger after 0.5 and 1.0% CO2 step-changes than after 1.5% CO2 step-change (10 sec vs 2 sec for T0). In CDN rats, this 1.5% CO2 hyperventilation was delayed, but this delay was shorter (5 sec) than in IR or XT rats inhalating 0.5 and 1.0% CO2. After ALM pretreatment, the amplitude of the ventilatory response to a same rise in PETCO2 was increased. T0 and T50 - T0 during 0.5 and 1.0% CO2 step-changes became identical to the time values obtained with the 1.5% CO2 mixture in untreated rats. Variations in amplitude and dynamics of the ventilatory responses to CO2 provoked by ALM pretreatment may be explained by an increased sensitivity of the peripheral chemoreceptors to CO2, T0 at the time of the weakest stimuli becoming equal to that observed for a higher hypercapnia and no longer different from the lung to carotid bodies circulation time. So, the delayed and smoothed responses to 0.5 and 1.0% CO2 in IR and XT rats were attributed to a PaCO2 too weak to stimulate the peripheral chemoreceptors. The latency and half response time were higher than in CDN rats due to a weaker induced difference in PETCO2. Hyperventilation dynamics changes induced by ALM allowed to differentiate between peripheral and central chemoreception in ventilatory control.