Involvement of nitric oxide and potassium channels in the bradykinin-induced vasodilatation in the rat kidney perfused ex situ.
The role of nitric oxide (NO), K(+) channels, and arachidonic acid metabolism, via cytochrome P450 and cyclooxygenase pathways, in the renal vasodilatory effect of bradykinin was examined in the isolated rat kidney perfused ex situ with a blood-free solution. Bradykinin (BK, 0.25-1.0 microM) induced a dose-dependent reduction of 10-35% in the relative renal vascular resistance (rRVR) of isolated kidneys preconstricted with phenylephrine (PHE, 0.17-0.35 microM). The vasodilating effect of 0.5 microM bradykinin was significantly inhibited by the nitric oxide synthase inhibitors, N(G)-nitro-L-arginine (95% inhibition) and N(G)-nitro-L-arginine methyl ester (45-75% inhibition). Clotrimazole, an inhibitor of cytochrome P450 pathway but not indomethacin, a cyclooxygenase inhibitor, reduced the renal vasodilator response to bradykinin by 84%. The nonspecific K(+) channel inhibitor, tetraethylammonium ion (TEA) and the selective inhibitor of Ca(2+)-activated K(+) channels, charybdotoxin (ChTX) greatly attenuated the vasodilator response to bradykinin by approximately 84% and 79%, respectively. These two K(+) channel inhibitors showed similar effects on vasodilatation induced by S-nitroso-acetyl-D,L-penicillamine (1 microM), a nitric oxide donor. The results suggest that bradykinin releases nitric oxide which, by opening potassium channels specifically the Ca(+)-dependent type, mediates the renal vasodilator response to bradykinin in the isolated kidney perfused ex situ.
Pompermayer
Kênia
K
Department of Physiology and Biophysics, ICB, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil.
Assreuy
Jamil
J
Vieira
Maria Aparecida Ribeiro
MA
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003022:Clotrimazole / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010477:Perfusion; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D007473:Ion Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D003022:Clotrimazole; D010396:Penicillamine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin