Kishi Y, Oniki T, Ashikaga T, Numano F
Third Department of Medicine, Tokyo Medical and Dental University, Japan.
Angiology. 1993 Jan;44(1):62-8. doi: 10.1177/000331979304400110.
The authors tested the hypothesis that ethanol or its metabolite acetaldehyde might interfere in cyclic guanosine monophosphate (GMP) metabolism in coronary smooth muscle cells. Ethanol at the physiologically relevant concentration of 4.0 mg/mL or more significantly decreased basal guanylate cyclase activity and inhibited activation of the enzyme by sodium nitroprusside (SNP) in cultured porcine coronary smooth muscle cells. Two isoforms of phosphodiesterase (PDE), cyclic GMP-specific form and calmodulin-stimulated form, were both inhibited by 12.0 mg/mL or more ethanol. Intact cell study revealed that although 12.0 mg/mL or more ethanol was needed to significantly decrease cyclic GMP accumulation in control cells, 4.0 mg/mL or more ethanol significantly inhibited the increase of cyclic GMP accumulation induced by 1 microns SNP. Acetaldehyde showed similar effects, but the concentrations involved were more than physiological. Thus, ethanol may decrease cellular cyclic GMP levels and attenuate cyclic GMP accumulation in response to SNP in coronary smooth muscle cells by inhibiting soluble guanylate cyclase activity at physiologically relevant concentrations.
作者检验了乙醇或其代谢产物乙醛可能干扰冠状动脉平滑肌细胞中环磷酸鸟苷（cGMP）代谢的假说。在培养的猪冠状动脉平滑肌细胞中，生理相关浓度为4.0mg/mL及以上的乙醇显著降低了基础鸟苷酸环化酶活性，并抑制了硝普钠（SNP）对该酶的激活作用。两种磷酸二酯酶（PDE）同工型，即cGMP特异性型和钙调蛋白刺激型，均被12.0mg/mL及以上的乙醇所抑制。完整细胞研究表明，虽然需要12.0mg/mL及以上的乙醇才能显著降低对照细胞中的cGMP积累，但4.0mg/mL及以上的乙醇能显著抑制1微摩尔SNP诱导的cGMP积累增加。乙醛表现出类似的作用，但所涉及的浓度超过了生理浓度。因此，乙醇可能通过在生理相关浓度下抑制可溶性鸟苷酸环化酶活性，降低冠状动脉平滑肌细胞中的细胞内cGMP水平，并减弱对SNP的cGMP积累反应。
