Role of the mediators in pulmonary hyperreactivity: the cocktail interaction hypothesis

Pulmonary hyperreactivity is a common feature in asthma. In the present study we investigated the possible role of different mediators in the genesis of this phenomenon. In particular the ability of prostaglandin D2 (PGD2), substance P (SP) and bradykinin (BK) to potentiate acetylcholine (ACh)-induced bronchospasm was assessed in anaesthetized and mechanically ventilated guinea-pigs. Threshold doses of PGD2, SP and BK significantly enhanced ACh-induced bronchospasm in normal guinea-pigs, even if a different trend in the onset and duration of the phenomenon was observed. Ovalbumin (OA) active sensitization modified the ability of the three compounds tested to positively interact with ACh. Beta-adrenoceptor blockade due to propranolol treatment increased the positive interaction between the three compounds and ACh. The role of PGD2, SP and BK in the genesis of pulmonary hyperreactivity is proposed and the relevance of mediator-mediator interaction during adrenergic imbalance is discussed.