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Signalling pathways in bradykinin‐ and nitric oxide‐induced hypotension in the normotensive rat; role of K + ‐channels
Author(s) -
Berg Torill,
Koteng Øyvind
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701246
Subject(s) - apamin , iberiotoxin , bradykinin , chemistry , nitric oxide , tetraethylammonium , channel blocker , charybdotoxin , medicine , pharmacology , glibenclamide , endocrinology , potassium channel , biochemistry , calcium , potassium , receptor , organic chemistry , diabetes mellitus
Bradykinin and nitric oxide (NO) are potent hypotensive agents. In the present study, the role of K + ‐channels in the signalling pathways responsible for their hypotensive action was investigated in normotensive, anaesthetized rats. The rats were treated with ion‐channel inhibitors before administration of bradykinin (2.8, 5.6, 28 and 56nmolkg −1 , i.v.) followed in some of the protocols by nitroprusside (1.1, 3.5, 7, 14, and 28nmolkg −1 , i.v.). No attenuation of the hypotensive response to bradykinin was detected for inhibitors of the Na‐K‐Cl‐cotransporter (30μmolkg −1 furosemide), the ATP‐sensitive K + ‐channel (40μmolkg −1 glibenclamide), high conductance Ca 2+ ‐activated K + ‐channel (180μmolkg −1 tetraethylammonium, 54μmolkg −1 tetrabutylammonium, 35nmolkg −1 iberiotoxin, 35nmolkg −1 charybdotoxin) or the low conductance Ca 2+ ‐activated K + ‐channel (74nmolkg −1 apamin). However, the voltage‐sensitive K + ‐channel ( I A ) inhibitor 4‐aminopyridine (4.05–40.5μmolkg −1 ) induced a concentration‐dependent ( P <0.0001) attenuation of the hypotensive response ( P <0.0001). Bradykinin had no effect on heart rate in anaesthetized rats and this observation was not altered by pretreatment with 4‐aminopyridine. 4‐Aminopyridine (53μmolkg −1 ) also significantly attenuated the hypotensive response to nitroprusside ( P <0.0003) without altering the heart rate concentration‐response curve. Of the two Ca 2+ ‐activated K + ‐channel inhibitors tested on nitroprusside‐induced hypotension, tetrabutylammonium induced a slight attenuation ( P <0.0101), whereas iberiotoxin had no effect. We therefore concluded that, although the acute hypotensive response to bradykinin in the normotensive rat is not mediated through nitric oxide synthesis, the hypotensive response to both agents was mediated through opening of voltage‐sensitive K + ‐channels ( I A ), resulting in a decrease in peripheral vascular resistance.