Negative inotropic effect of bradykinin in porcine isolated atrial trabeculae: role of nitric oxide.
OBJECTIVE
To investigate whether bradykinin affects cardiac contractility independently of its effects on coronary flow and noradrenaline release, and whether such inotropic effects, if present, are mediated via nitric oxide (NO).


METHODS
Right atrial trabeculae were obtained from 35 pigs, suspended in organ baths and attached to isometric transducers. Resting tension was set at approximately 750 mg and tissues were paced at 1.5 Hz. Tissue viability was checked by constructing a concentration response curve (CRC) to noradrenaline. Next, CRCs were constructed to bradykinin, either under baseline conditions or after pre-stimulation with the positive inotropic agent forskolin (1 or 10 micromol/l), in the absence or presence of the bradykinin type 2 (B2) receptor antagonist D-Arg [Hyp3-Thi5, d-Tic7, Oic8]-bradykinin (Hoe 140) (1 micromol/l), the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) (100 micromol/l) and/or the NO scavenger hydroxocobalamin (200 micromol/l).


RESULTS
Bradykinin exerted a negative inotropic effect, both with and without forskolin pre-stimulation, reducing contractility by maximally 22 +/- 3.6% (mean +/- SEM) and 23 +/- 3.6%, respectively (pEC50 8.37 +/- 0.23 and 8.62 +/- 0.22, respectively). L-NAME reduced this effect in pre-stimulated, but not in unstimulated, trabeculae. Hoe 140 and hydroxocobalamin fully blocked the inotropic effect of bradykinin.


CONCLUSIONS
Bradykinin induces a modest negative inotropic effect in porcine atrial trabeculae that is mediated via B2 receptors and NO. The inconsistent results obtained with L-NAME suggest that it depends on NO synthesized de novo and/or NO from storage sites.
Tom
B
B
Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
de Vries
R
R
Saxena
P R
PR
Danser
A H
AH
D000818:Animals; D016275:Atrial Function / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006879:Hydroxocobalamin / Q000494:pharmacology; D066298:In Vitro Techniques; D000432:Methanol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D013552:Swine
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D005576:Colforsin; D009569:Nitric Oxide; D006879:Hydroxocobalamin; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D000432:Methanol