Modulatory effects of ketamine on catecholamine efflux from in vivo cardiac sympathetic nerve endings in cats

doi:10.1016/S0304-3940(02)00208-2

Neuroscience Letters

Volume 324, Issue 3, 24 May 2002, Pages 232-236

https://doi.org/10.1016/S0304-3940(02)00208-2 Get rights and content

Abstract

With the use of the microdialysis technique, we examined the modulatory effect of ketamine on catecholamine efflux from in vivo cardiac sympathetic nerve endings. A dialysis probe was implanted in the left ventricular myocardium, and dialysate norepinephrine (NE) levels in anesthetized cats were measured with liquid chromatogram–electrical detection. A 60-min occlusion of the left anterior descending coronary artery caused increases in dialysate NE levels. Through the dialysis probe, locally applied ketamine (10 mM) augmented the dialysate NE responses to coronary occlusion in the presence and absence of desipramine (membrane NE transport blocker). Thus, the ketamine-induced NE increment is not mediated through the neuronal NE transporter. The sympathomimetic action of ketamine may augment the NE efflux evoked by myocardial ischemia.

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Acknowledgements

This study was by the program for Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research, Health Sciences Research Grant for Advanced Medical Technology from the Ministry of Health and Welfare of Japan, Ground-Based Research Grant for the Space Utilization promoted by NASDA (National Development Agency of Japan) and Japan Space Forum.

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Citation Excerpt :
Near the nerve ending and after stimulation, the myocardium NE concentration could be even higher. The range of NE concentration in rat and cat myocardium were around 0.1 µM and 10,000 pg/ml (approximately 10 µM as NE molecular weight is 169 g/mol) respectively [23,24]. Cleavage of caspase 3 plays a key role during apoptosis.
Prolonged sympathetic activation is damaging to the heart. Recent findings suggest that norepinephrine (NE) may contribute to the apoptotic cardiac cell loss. This study investigated high doses NE apoptotic effect on cardiac fibroblasts (CF) culture and compared the anti-apoptotic effect of α and β (selective and non-selective) adrenergic receptor antagonists.
Rat CF were cultured in the presence of NE (1 to 100 µM) for 48 h. bax and bcl_XL genes expression were measured by real-time quantitative PCR method. Cell viability percentage, apoptotic cell percentage and caspase 3 activity was measured by MTT assay, flow cytometric method and caspase 3 flurogenic assay kit respectively. NE (100 µM) increased bax gene expression by 1.96 ± 0.96 fold while bcl_XL gene decreased by 0.53 ± 0.15 fold when compared with the control group (p < 0.01). The apoptotic cell percentage increased significantly from 5.09 ± 2.94% in control group to 31.48 ± 6.35% (p < 0.01) with NE and the caspase 3 activity increased from 1432.2 ± 658.8 in the control group to 5162 ± 2028.6 (OD/µg protein, p < 0.05). Addition of carvedilol (non-selective β blocker with α-blockade activity), doxazosin (α blocker), metoprolol (β1 selective blocker) and propranolol (non-selective β blocker) were not capable of inhibiting the apoptotic effect of high dose NE on CF.
High dose NE has cytotoxic and apoptotic effect on CF. The process involved the activation of caspase 3, up-regulation of pro-apoptotic gene bax and down-regulation of anti-apoptotic gene bcl_XL. Both non-selective and selective adrenergic receptor antagonists tested were not capable of inhibiting the apoptotic effect of high dose NE on CF.
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Modulatory effects of ketamine on catecholamine efflux from in vivo cardiac sympathetic nerve endings in cats

Abstract

Section snippets

Acknowledgements

Res. Vet. ci.

J. Chromatogr. B Biomed. Sci. Appl.

J. Auton. Nerv. Syst.

J. Auton. Nerv. Syst.

Neuroscience

Eur. J. Pharmacol.

Trends Neurosci.

J. Chromatogr. B Biomed. Appl.

Brain Res.

Brain Res. Bull.