Does ageing modify ventilatory responses to dopamine in anaesthetised rats breathing spontaneously?
Dopamine has been widely used in humans in the management of cardiocirculatory shock, and its inhibitory effect on ventilation has received particular attention in clinical situations more prevalent in the elderly. Dopamine has been extensively studied at the carotid body in adult animals but little is known in aged animals. We investigated the ventilatory responses caused by dopamine in 3 and 24 months old rats.Cumulative intracarotid bolus injections of dopamine were performed in anaesthetised and vagotomised rats, in the absence and in the presence of i.v. infusions of domperidone (23.5-1175 nmol Kg(-1) min(-1)). Airflow (V), tidal volume (V(T)), respiratory rate (f), arterial blood pressure and heart rate were monitored and respiratory minute volume (V(E)) calculated. Basal values of V(E) were lower in 24 months rats (322.9+/-18.8 mL Kg(-1) min(-1)) than in 3 months old rats (442.5+/-24.2 mL Kg(-1) min(-1)), mainly due to reductions in V(T). The dose-dependent decreases caused by dopamine (3-100 nmol) in V(T), f and V(E), were totally prevented by section of the carotid sinus nerve and were not modified by ageing. The maximal % antagonism of the inhibitory effect of dopamine on V(E) caused by domperidone was similar in both 3 (74.6+/-2.7) and 24 (70.7+/-0.8) months old rats. Domperidone alone, increased basal V(E) by 59.6+/-16.6 mL min(-1) Kg(-1), and by 11.8+/-1.2 mL min(-1) Kg(-1), respectively in 3 and 24 months old rats (p<0.01).The inhibitory basal tonus caused by dopamine in ventilation was reduced in aged rats, although the decrease in V(E) caused by its exogenous administration remained unchanged.
Monteiro
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Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria, 130, 1169-056 Lisboa, Portugal. teresa.monteiro@fcm.unl.pt
Obeso
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Gonzalez
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Monteiro
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D000375:Aging / Q000502:physiology*; D000758:Anesthesia; D000818:Animals; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D012123:Pulmonary Ventilation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012119:Respiration
D018492:Dopamine Antagonists; D004294:Domperidone; D004298:Dopamine