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Concomitant effect of dopamine and acetylcholine on carotid body chemosensory response to hypoxia in the cat
Respiratory Researchvolume 2, Article number: P21 (2001)
Dopamine (DA) and acetylcholine (Ach) are released from the carotid body chemoreceptor cells under basal conditions and stimulation by hypoxia. The role of DA and Ach in the control of the carotid sinus nerve chemosensory discharge (CSND) are still under debate. Here we tested the hypothesis that DA is inhibitory to the CSND and the effect is reversed by Ach. The CSND was recorded in 2 groups of anesthetized and artificially ventilated adult cats. The treatment group received alpha-methyl-paratyrosine (250 mg/kg) and reserpine (5 mg/kg) administered intraperitoneally, respectively 2.5 h and 12 h prior to the experiment in order to minimize the contribution of endogenous DA. The control group was injected with normal saline. CSND and arterial blood pressure (ABP) were recorded 1) at baseline 2) with a continuous iv infusion of DA, 5 μg/kg/min and 3) with a continuous infusion of Ach (25 μg/kg/min), while DA infusion was ongoing. DA & Ach infusions were initiated in room air. At baseline and 10 min into each infusion, the FIO2 was switched from room air to 8% O2 in N2 for 2–3 min and then to 100% O2 for 2–3 min.
One min into DA infusion, CSND was decreased from 3.1 ± 0.4–0.8 ± 0.4 imp/s (P < 0.01) in controls and from 3.2 ± 0.8–0.3 ± 0.2 (imp/s, P < 0.01) in the treatment group. Up to 10 min into DA infusion, the CSND was restored in controls but still significantly inhibited in treated cats in room air and hyperoxia. The mean ± SEM CSND (impulses/sec) and ABP (mmHg) at steady state are listed in Table 1 overleaf. Compared with DA alone, DA+ACh appears to increase the CSND in control cats breathing room air as well as in treated cats breathing room air or 100% O2. Compared with DA, ABP was particularly depressed during DA+Ach in the treatment group breathing room air. The CSND in hypoxia was unchanged throughout the experiment.
It is concluded that endogenous DA regulates the basal CSND and Ach may be capable of restoring the activity previously inhibited by DA. The effect of Ach appears to be independent from ABP changes in room air for control cats and in hyperoxia for treated cats. In the experimental conditions, neither DA nor DA+Ach appear to modify the CSND response to hypoxia.
Supported by Téléthon de la Recherche sur les Maladies Infantiles. RK is a Parker B. Francis Fellow in Pulmonary Research.