Possible involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressor responses to platelet activating factor (PAF) in rats

1 Tn anaesthetized rats, platelet activating factor (PAF; 1 mug kg(-1)) dec reased mean arterial blood pressure by around 60 mmHg (n = 18). This depres sor response was completely blocked by the PAF antagonist, CV-6209 (1 mg kg (-1)), indicating the role of PAF-specific receptor in the response. 2 N-G-nitro-L-arginine methyl ester (L-NAME; 50 mg kg(-1)), an NO synthase inhibitor, profoundly elevated systemic blood pressure (n=19), indicating a n important role of NO in the basal blood pressure regulation. The depresso r response to PAF (1 pg kg(-1)) normalized against that to sodium nitroprus side (SNP) (10 mug kg(-1)) was not substantially different between rats tre ated without and with L-NAME (n=4). In contrast, the depressor effect of ac etylcholine (0.03-1.0 mug kg(-1)) normalized against that of SNP (10 mug kg (-1)) was significantly attenuated by r-NAME (n=5). 3 Charybdotoxin (0.4 mg kg(-1)) plus apamin (0.2 mg kg(-1)) significantly a ttenuated the depressor response to PAF (1 mug kg(-1)) (n=5) without affect ing the blood pressure change due to SNP (1 mg kg(-1)) (n=3). Charybdotoxin (0,4 mg kg(-1)) (n=4) or apamin (0.2 mg kg(-1)) (n=4) alone did not affect the PAF-induced depressor response. 4 These findings suggest that EDHF may make a significant contribution to t he depressor response to PAF in rats. Although NO plays the determinant rol e in the basal blood pressure regulation, its contribution to PAF-produced depressor response seems to be less as compared with that to the depressor response to acetylcholine.