PROTECTIVE EFFECT OF FUROSEMIDE COMBINED WITH NONSTEROIDAL ANTIINFLAMMATORY DRUGS ADMINISTERED BY INHALATION ROUTE ON GUINEA-PIGS ANAPHYLAXIS MODEL

The exposure of ovalbumin sensitized guinea-pig to an areosol of the s pecific antigen causes a respiratory crisis in approximately 100 s (di spnoea time) associated with a substantial increase in Blood concentra tion of both histamine (from 27.5 +/- 1.8 ng/ml to 1570 +/- 26 ng/ml; n = 8) and thromboxane B-2 (TXB(2), from 0.52 +/- 0.03 ng/ml to 18.1 /- 0.6 ng/ml; n = 8). The aerosol treatment of the animals (20 min) wi th furosemide (CAS 54-31-9, frusemide, FRU), nimesulide (CAS 51803-78- 2, NIM), acetylsalicylic acid (CAS 50-78-2, ASA) and indometacin (CAS 53-86-1, INDO) at the concentrations of 1-3-10 and 30 mg/ml, before ov albumin challenge, brought about an attenuation of anaphylactic respon se. The rank order of potency for the prolongation of dyspnoea time wa s FRU > NIM > ASA > INDO. In these experiments blood evaluation perfor med at the peak of the dyspnoea time for histamine concentration in th e treated animals indicated that whereas FRU (ED(25) = 2.14 mg/ml (1.9 7-2.38) and NIM (ED(25) = 2.74 mg/ml (2.37-3.19)) were equiactive in r educing the release of histamine, ASA and INDO were devoid of this act ivity. On the contrary, the results obtained with ASA and INDO indicat ed a greater intrinsic activity in antagonising TXB(2) formation than that shown by the log-dose response curves of NIM and FRU. In another series of experiments the interaction of FRU with the other anti-infla mmatory drugs in protecting guinea-pig from immune bronchoconstriction has been evaluated using the combination of two equiactive closes. Th e mixture considered were FRU + NIM, FRU + INDO and FRU + ASA. The res ults obtained indicated that FRU interacts positively with the three n on-steroidal anti-inflammatory drugs in delaying the onset of the dysp noeic crisis in guinea-pig. However, when FRU was combined with NIM th e gain obtained (209%) appeared superior to that reached when FRU was combined with ASA (180%) or INDO (126%). Taken together these results suggest that non-steroidal anti-inflammatory compounds given by aeroso l may represent a valid pharmacological intervention in protecting gui nea-pig from anaphylactic bronchoconstriction.