Angiotensin peptides attenuate platelet-activating factor-induced inflammatory activity in rats.
Angiotensin (Ang)--a peptide that is part of the renin-angiotensin system-induces vasoconstriction and a subsequent increase in blood pressure; Ang peptides, especially AngII, can also act as potent pro-inflammatory mediators. Platelet-activating factor (PAF) is a potent phospholipid mediator that is implicated in many inflammatory diseases. In this study, we investigated the effects of Ang peptides (AngII, AngIII, and AngIV) on PAF-induced inflammatory activity. In experiments using a rat hind-paw oedema model, AngII markedly and dose-dependently attenuated the paw oedema induced by PAF. The inhibitory effects of AngIII and AngIV on PAF-induced paw oedema were lower than that of AngII. Two Ang receptors, the AT1 and AT2 receptors, did not affect the AngII-mediated attenuation of PAF-induced paw oedema. Moreover, intrinsic tyrosine fluorescence studies demonstrated that AngII, AngIII, and AngIV interact with PAF, and that their affinities were closely correlated with their inhibitory effects on PAF-induced rat paw oedema. Also, AngII interacted with metabolite/precursor of PAF (lyso-PAF), and an oxidized phospholipid, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), which bears a marked structural resemblance to PAF. Furthermore, POVPC dose-dependently inhibited AngII-mediated attenuation of PAF-induced paw oedema. These results suggest that Ang peptides can attenuate PAF-induced inflammatory activity through binding to PAF and lyso-PAF in rats. Therefore, Ang peptides may be closely involved in the regulation of many inflammatory diseases caused by PAF.
Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan. Electronic address: a-sato@iwakimu.ac.jp.
Akira
A
Sato
Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan.
Izumi
I
Yokoyama
Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan.
Keiichi
K
Ebina
D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D004487:Edema / Q000139:chemically induced / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*
D000809:Angiotensins; D010455:Peptides; D010972:Platelet Activating Factor; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
Angiotensin peptide; Inflammation; Interaction; Oxidized phospholipid; Platelet-activating factor