Premium
Possible involvement of endothelium‐derived hyperpolarizing factor (EDHF) in the depressor responses to platelet activating factor (PAF) in rats
Author(s) -
Tanaka Yoshio,
Hayakawa Sachiko,
Imai Toshiyasu,
Akutsu Aya,
Hirano Haruko,
Tanaka Hikaru,
Nakahara Tsutomu,
Ishii Kunio,
Shigenobu Koki
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703681
Subject(s) - apamin , chemistry , sodium nitroprusside , charybdotoxin , endocrinology , platelet activating factor , medicine , blood pressure , antagonist , nitric oxide , receptor , biochemistry , potassium channel
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.British Journal of Pharmacology (2000) 131 , 1113–1120; doi: 10.1038/sj.bjp.0703681