Negative inotropic effect of bradykinin in porcine isolated atrial trabeculae: role of nitric oxide

Objectives 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 mu mol/l), in the absence or presence of the bradykinin type 2 (B-2) receptor antagonist D-Arg [Hyp(3)-Thi(5), d-Tic(7), Oic(8)]-bradykinin (Hoe 140) (1 mu mol/l), the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) (100 mu mol/l) and/or the NO scavenger hydroxocobalamin (200 mu mol/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 (pEC(50) 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 B-2 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. (C) 2001 Lippincott Williams & Wilkins.