Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ventilation was measured by a plethysmographic method in awake mice before and after intraperitoneal injection of neuroleptic drugs to test the hypothesis that dopaminergic mechanisms modulate control of breathing in this species. Dose-dependent augmentation of ventilation at rest and during hypoxia, and reduced ventilation during hypercapnia was demonstrated for haloperidol, droperidol, prochlorperazine and chlorpromazine (P less than 0.05 or less for each drug). Doses of drugs causing maximal increase of the ventilatory response to hypoxia were linearly related (r = 0.98, P less than 0.001) to in vitro affinity of the drugs for dopamine receptors. Despite presumed equal dopamine-receptor blockade, the drugs had unequal effects on the ventilatory response to hypoxia. Droperidol augmented hypoxic ventilation to 290% of the control value, chlorpromazine to 250% control, prochlorperazine to 190% control and haloperidol to 120% control. These differences in efficacy were in the same order as the affinities of the drugs for alpha-adrenoceptors. The effect of combined haloperidol (90 nmol kg-1) and varying doses of phentolamine (175-900 nmol kg-1) was assessed to test the hypothesis that alpha-antagonism was a factor in determining the increase in ventilation following dopamine blockade. Phentolamine caused dose-dependent augmentation of the ventilatory effects of haloperidol (P less than 0.01) but had no ventilatory effect when given alone. Carotid body resection in anaesthetized mice abolished the stimulation of hypoxic ventilation caused by droperidol. It is concluded that dopaminergic mechanisms in the carotid body modulate ventilatory control in the awake mouse. The drugs most effective in augmenting hypoxic ventilation are those that block both dopamine and alpha-adrenoceptors.
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PMID:Ventilatory stimulation by dopamine-receptor antagonists in the mouse. 286 37

We determined the effects of chronic repetitive hypoxia and hypercapnic hypoxia on systemic and pulmonary hemodynamics using an animal model simulating sleep apnea syndrome (SAS). Fifty-six rats were divided into the hypoxia (Pao2 44-46Torr) and the hypercapnic hypoxia (Pao2 44-46Torr, Paco2 48-49Torr) group. The hypoxic gas or the hypercapnic hypoxic gas was flushed into the chamber for 1 min, then air was flushed allowing return of gas fractions to ambient levels for 3 min. Each cycle was repeated 6h/day for 5 weeks. In the hypoxia group, there was no significant difference in baseline blood pressure (BP) and heart rate (HR) between controls and the exposure group. Only HR increased transiently during hypoxia in both controls and the exposure group. RV/(LV + S) did not change after 5 weeks of exposure. In the hypercapnic hypoxia group, there was no significant difference in baseline BP and HR between controls and the exposure group. However, acute BP elevation and transient bradycardia were induced during hypercapnic hypoxia, and the magnitude of the changes increased with an increase in the exposure period. RV/(LV + S) increased after 5 weeks of exposure. Phentolamine attenuated acute BP elevation and atropine abolished bradycardia, suggesting an increased sympathetic and parasympathetic tone. The results suggest that hypercapnia associated with hypoxia plays an important role in developing cardiovascular changes in SAS.
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PMID:[Effects of chronic repetitive hypercapnic hypoxia on systemic and pulmonary hemodynamics in a rat model]. 1945 55