Vasoconstrictor actions of methamphetamine stereoisomers in isolated porcine coronary artery

Amy Herbert, Kenneth Broadley, Emma Kidd, William Ford. Cardiff University, Cardiff, United Kingdom.

Methamphetamine (MA) is a highly-addictive stimulant. To decrease MA abuse, many precursors of its synthesis are now controlled substances. (+)-MA is the isomer usually abused, although synthetic pathways via unregulated precursors produce racemic and (−)-MA (Mendelson et al., 2006).The initial sign of MA abuse is hypertension, which ultimately results in organ damage (Turnipseed et al., 2003). MA is believed to act as an indirectly acting sympathomimetic amine (ISA) stimulating postsynaptic α- and β- adrenergic receptors (McGuinness, 2006). The pharmacological effects of MA in the coronary artery are unexplored. This study evaluates whether the vasoactive response to MA stereoisomers in porcine coronary artery can be attributed to ISA mechanisms.

Left anterior descending porcine coronary artery rings, approximately 5mm in length, were mounted on wires in an organ bath filled with Krebs solution at 37°C, aerated with O2 and 5% CO2. An initial resting tension of 5g was applied after equilibration for 1 hour. Cumulative concentration-response curves (CRCs) to (+)- and (−)-MA (1-10,000μM) were obtained. Adrenoceptor subtypes involved in the responses to (+)- and (−)-MA were evaluated using 3μM DL-propranolol (non-selective β-adrenoceptor antagonist) and 1μM prazosin (α1-adrenoceptor antagonist). Isometric tension was recorded on a PowerLab/4SP computer system and plotted as a % response to 60mM isotonic KCl. Statistical comparisons used one way ANOVA and Dunnett post-test or unpaired t-tests.
(+)- and (−)-MA produced equipotent concentration-dependent vasoconstriction. The maximum responses (at 3mM MA) and log EC50 values were not significantly different in the absence or presence of adrenergic receptor antagonists or between stereoisomers (Table 1).

Table 1: Effects of adrenergic receptor antagonists on the maximum responses and log EC50 values of (+)-MA and (−)-MA in porcine coronary arteries. Data represent mean ± s.e.m.

Adrenoceptors of the α1- and β- subtypes are not responsible for vasoconstriction by MA stereoisomers in porcine coronary artery, which does not therefore act as an ISA.

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Supported by the British Heart Foundation.