Effect of quercetin on plasma extravasation in rat CNS and dura mater by ACE and NEP inhibition.
The effects of quercetin on substance P-induced plasma protein extravasation (PE) in the rat dura mater, cerebellum, olfactory bulb and cortex and also its modulation by endopeptidases, angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) were studied. PE was assessed by photometric measurement of extravasated Evans blue. Substance P (SP) and NEP or ACE inhibitors increased the PE in dura mater. Pretreatment with captopril or phosphoramidon potentiated PE induced by SP in the dura mater and cerebellum, respectively. Quercetin increased the PE in the dura mater, cerebellum and cortex. Further results suggested that the PE induced by SP in the dura mater was enhanced by pretreatment with quercetin, similar to that observed with selective peptidase inhibitors. Quercetin-stimulated extravasation in all tissues was abolished by NK-1 receptor blockade. These results suggest that quercetin increases PE in the dura mater and CNS tissues by inhibiting NEP and/or ACE, showing that the effect induced in the dura mater, cerebellum and cortex occurs through endogenous SP accumulation.
Cyrino
Luiz A R
LA
Department of Physiology, CCB, Federal University of Santa Catarina, 88040-900 Florianópolis, Brazil.
Cardoso
Ronie C F
RC
Hackl
Luciane P N
LP
Nicolau
Mauro
M
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002490:Central Nervous System / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002531:Cerebellum / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D004388:Dura Mater / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005070:Evans Blue / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000517:prevention & control; D006020:Glycopeptides / Q000494:pharmacology; D007601:Jugular Veins / Q000187:drug effects; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D064729:Neurokinin-1 Receptor Antagonists; D009830:Olfactory Bulb / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects* / Q000378:metabolism; D011794:Quercetin / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000378:metabolism
D006020:Glycopeptides; D064729:Neurokinin-1 Receptor Antagonists; D013373:Substance P; D005070:Evans Blue; D002216:Captopril; D011794:Quercetin; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; C008890:phosphoramidon