The role of the endocardium in the facilitatory effect of bradykinin on electrically-induced release of noradrenaline in rat cardiac ventricle.
1. The present investigation was undertaken to study the role of bradykinin in noradrenaline release from the ventricle of the rat induced by electrical stimulation. Slices of the left ventricle of adult Wistar rats with or without endocardium were previously loaded with 0.2 microM [3H]-noradrenaline and washed out before electrical stimulation was applied. 2. Bradykinin (0.1-100 nM) concentration-dependently increased tritium release evoked by electrical stimulation (EC50 = 3.5 (1.2-10.2) nM; n = 12). The angiotensin converting enzyme inhibitor, captopril (1 microM), which per se had no effect on tritium release, caused a marked enhancement of the bradykinin facilitatory effect, shifting the concentration-response curve of bradykinin to the left by about one log unit. The compound Hoe 140, a selective inhibitor of B2-bradykinin receptors, competitively antagonized the effect of bradykinin, indicating the involvement of these receptors in the action of bradykinin. 3. In endocardium-free ventricle, bradykinin had no effect either in the absence or in the presence of captopril. 4. These results show that: (1) bradykinin is able to facilitate noradrenaline release evoked by electrical stimulation of the rat ventricle through activation of B2-bradykinin receptors located on endocardial cells; (2) this action of bradykinin which is markedly potentiated by the inhibition of the angiotensin-converting enzyme seems to be exerted through the release of some factor which is formed in the endocardium and diffuses into the myocardium where it acts.
Vaz-da-Silva
M
M
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Portugal.
Magina
S
S
Domingues-Costa
A
A
Moura
D
D
GuimarãesS
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D004558:Electric Stimulation; D004699:Endocardium / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines; D016276:Ventricular Function
D000806:Angiotensin-Converting Enzyme Inhibitors; D044005:Tetrahydroisoquinolines; C076640:bradykinin, Hyp(3)-Thi(5)-Tic(7)-Oic(8)-desArg(9)-; C065679:icatibant; D002216:Captopril; D001920:Bradykinin; D009638:Norepinephrine