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Bradykinin modulation of isolated rabbit heart function is mediated by intrinsic cardiac neurons
Journal article   Open access   Peer reviewed

Bradykinin modulation of isolated rabbit heart function is mediated by intrinsic cardiac neurons

I Izrailtyan and J Y Kresh
Cardiovascular research, v 33(3), pp 641-649
Mar 1997
DOI: https://doi.org/10.1016/S0008-6363(96)00267-2
PMID: 9093534
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/S0008-6363(96)00267-2View
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Abstract

Rabbits Ventricular Pressure - drug effects Adrenergic beta-Agonists - pharmacology Atropine - pharmacology Timolol - pharmacology Nicotinic Antagonists - pharmacology Parasympatholytics - pharmacology Dobutamine - pharmacology Heart Rate - drug effects Hexamethonium - pharmacology Animals Perfusion Parasympathetic Nervous System - drug effects Heart - drug effects Tetrodotoxin - pharmacology Neurons - drug effects Bradykinin - pharmacology Heart - innervation
Bradykinin (BK) is an endogenous peptide exerting a potent influence on the behavior of the heart. The local regulatory mechanisms responsible for BK modulation of cardiac automaticity and contractility remain poorly understood. The role of the intrinsic cardiac nervous system (ICNS) in mediating the BK-induced regulatory effect was investigated. Heart rate (HR) and intramyocardial pressure (IMP) changes in response to BK (1.2-80 nmol) were studied in isolated rabbit hearts (n = 37). The intrinsic neural mechanisms underlying the cardiac effects of BK were characterized by use of atropine (ATR, 10(-6) M), timolol (TIM, 10(-5) M), hexamethonium (HEX, 10(-4) M), and tetrodotoxin (TTX, 10(-7) M). Modulation of beta-adrenergic tone by dobutamine (DOB, 1.6 x 10(-6) M) was used to expose the physiological importance of intrinsic cholinergic systems in mediating the cardiac action of BK. A single dose of BK induced an increase in IMP and a biphasic HR response. The negative chronotropic response to BK was correlated with negative HR change induced by nicotine activation of ICNS. BK-elicited 'bradycardia' was abolished by ATR and TTX, and attenuated (approximately 50%) by HEX. ATR and TTX potentiated the positive HR-response which was not affected by TIM. BK selectively antagonized [by 48.1(5.1)%] the DOB-induced tachycardia but did not modify the accompanied inotropic potentiation. These findings are the first demonstration that in the autonomically decentralized heart, the negative chronotropic action of BK is mediated by intrinsic cardiac cholinergic neurons. It would appear that the intrinsic neural network response, and not merely the BK-induced potentiation of cardiac postganglionic neural activity is involved in the local neuromodulatory action of BK. This intrinsic cardiac regulatory mechanism seems to play a major role in mitigating the adrenergically induced tachycardia, thus endowing this peptide with the capacity for cardioprotection.

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Web of Science research areas
Cardiac & Cardiovascular Systems
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