Changes in paw oedema triggered via bradykinin B(1) and B(2) receptors in streptozotocin-diabetic rats.
The present study investigated hind paw oedema mediated by bradykinin B(1) and B(2) receptors in streptozotocin-diabetic rats. Paw oedema induced by intraplantar (i.pl.) injection of bradykinin or the selective bradykinin B(2) receptor agonist, Tyrosine(8)-bradykinin ([Tyr(8)]bradykinin) (both 3 nmol/paw), was significantly reduced at 4 weeks after streptozotocin treatment (34 +/- 8% and 40 +/- 7%). At 6 weeks after streptozotocin, when paw oedema caused by substance P or prostaglandin E(2) (both 10 nmol/paw) was unchanged, inhibition of bradykinin B(2) receptor-mediated oedema was maximal (66 +/- 6% and 72 +/ -2%, for bradykinin and [Tyr(8)]bradykinin, respectively). The selective bradykinin B(1) receptor agonist, [des-Arg(9)]bradykinin (100 nmol/paw), induced only slight paw oedema in non-diabetic controls. Responses to [des-Arg(9)]bradykinin were markedly enhanced 8 weeks after streptozotocin (from 0.09 +/- 0.01 to 0.38 +/- 0.05 ml), less so at 10 weeks (0.22 +/- 0.03 ml), and returning to basal values at 12 weeks (0.11 +/- 0.03 ml). Treatment with insulin protamine zinc (1-3 U/day/7 weeks, s.c.) did not reverse the inhibition of responses to [Tyr(8)]bradykinin or the potentiation of responses to [des-Arg(9)]bradykinin seen at 8 weeks. Thus, streptozotocin-induced diabetes induces long-lasting alterations in oedematogenic responsiveness to kinins in the rat, characterized by marked reduction of oedema involving activation of bradykinin B(2) receptors, associated with enhancement of bradykinin B(1) receptor-mediated oedema.
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, 88015-420, SC, Florianópolis, Brazil.
M M
MM
Campos
D A
DA
Cabrini
A H
AH
Cardozo
G A
GA
Rae
J H
JH
Toro
J B
JB
Calixto
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015232:Dinoprostone / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000473:pathology*; D006614:Hindlimb; D007004:Hypoglycemic Agents / Q000494:pharmacology; D049528:Insulin, Long-Acting / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors
D065168:Bradykinin Receptor Antagonists; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C102309:bradykinin, Tyr(8)-; C024626:bradykinin, des-Arg(9)-; D013373:Substance P; D015232:Dinoprostone; D001920:Bradykinin