Possible involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressor responses to platelet activating factor (PAF) in rats.
1. In anaesthetized rats, platelet activating factor (PAF; 1 microg 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. 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 an important role of NO in the basal blood pressure regulation. The depressor response to PAF (1 microg kg(-1)) normalized against that to sodium nitroprusside (SNP) (10 microg 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 microg kg(-1)) normalized against that of SNP (10 microg kg(-1)) was significantly attenuated by L-NAME (n=5). 3. Charybdotoxin (0.4 mg kg(-1)) plus apamin (0.2 mg kg(-1)) significantly attenuated the depressor response to PAF (1 microg 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. 4. 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.
Tanaka
Y
Y
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan.
Hayakawa
S
S
Imai
T
T
Akutsu
A
A
Hirano
H
H
Tanaka
H
H
Nakahara
T
T
Ishii
K
K
Shigenobu
K
K
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001685:Biological Factors / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D003864:Depression, Chemical; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D001685:Biological Factors; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C067410:endothelium-dependent hyperpolarization factor; C053321:CV 6209; D018999:Charybdotoxin; D001030:Apamin; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester