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

摘要

class="enumerated" style="list-style-type:decimal">In anaesthetized rats, platelet activating factor (PAF; 1 μg kg⁻¹) decreased mean arterial blood pressure by around 60 mmHg (n=18). This depressor response was completely blocked by the PAF antagonist, CV-6209 (1 mg kg⁻¹), indicating the role of PAF-specific receptor in the response.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 an important role of NO in the basal blood pressure regulation. The depressor response to PAF (1 μg kg⁻¹) normalized against that to sodium nitroprusside (SNP) (10 μg kg⁻¹) was not substantially different between rats treated without and with L-NAME (n=4). In contrast, the depressor effect of acetylcholine (0.03–1.0 μg kg⁻¹) normalized against that of SNP (10 μg kg⁻¹) was significantly attenuated by L-NAME (n=5).Charybdotoxin (0.4 mg kg⁻¹) plus apamin (0.2 mg kg⁻¹) significantly attenuated the depressor response to PAF (1 μg kg⁻¹) (n=5) without affecting 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.These findings suggest that EDHF may make a significant contribution to the depressor response to PAF in rats. Although NO plays the determinant role 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.