CAS Induced by Intracoronary Acetylcholine is Not Always Associated with Endothelial Dysfunction

By Seung-Woon Rha, MD, PhD; Director, Cardiovascular Center, Korea University Guro Hospital
Kang-Yin Chen, MD, PhD; Cardiology Department, the Second Hospital of Tianjin Medical University

Coronary artery spasm (CAS) plays an important role in the pathogenesis of vasospastic angina and acute coronary syndrome, which both are initiated from endothelial dysfunction. Therefore, before we launched the present study, our initial expectation was that patients with diabetes mellitus (DM) should have a higher rate of CAS compared to those without.

Actually, before the present study, two of our articles have been published regarding the associations between cardiovascular risk factors and CAS.1,2 In one paper, we evaluated the incidence and characteristics of CAS in patients with peripheral arterial disease (PAD), which is considered to be a coronary artery disease equivalent. This paper showed that patients with PAD have a higher propensity for acetylcholine (ACh)-induced CAS, although they don’t have coronary atherosclerotic lesions on the coronary angiogram. The study seems to support the theory that PAD is associated with endothelial dysfunction.1

However, our other study showed that hypertension and uncontrolled blood pressure are negatively associated with CAS. Therefore, the second study suggests that the mechanisms and risk factors of CAS may be significantly different from those of coronary artery disease.2 Similarly, the present study showed that despite the expected endothelial dysfunction in DM patients, DM and the status of blood sugar control are not associated with significant CAS.

The discrepancy between these three papers pushes us to reconsider the relationship between endothelial dysfunction and CAS induced by intracoronary ACh provocation. ACh has dual effects on coronary artery tone depending on their intracoronary concentration. The normal response to ACh is vasodilation at small doses and vasoconstriction at higher doses when the direct vasoconstrictor effect of ACh overwhelms the stimulation of nitric oxide release. Thus, ACh-induced CAS in these three studies, we feel, does not necessarily signify endothelial dysfunction. Also, the present study does not contradict the well-established conception that DM is closely associated with endothelial dysfunction. Due to the nature of retrospective analyses, as we have mentioned in the discussion section, some important confounders might have been ignored. We hope the readers will consider the conclusion of the present study with these thoughts in mind.

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  1. Chen KY, Rha SW, Li YJ, Poddar KL, Jin Z, Minami Y, Wang L, Li GP, Saito S, Park JH, Na JO, Choi CU, Lim HE, Kim JW, Kim EJ, Park CG, Seo HS, Oh DJ. Peripheral arterial disease is associated with coronary artery spasm as assessed by an intracoronary acetylcholine provocation test. Clin Exp Pharmacol Physiol. 2009;36:e78-e82.
  2. Chen KY, Rha SW, Li YJ, Poddar KL, Jin Z, Minami Y, Saito S, Park JH, Na JO, Choi CU, Lim HE, Kim JW, Kim EJ, Park CG, Seo HS, Oh DJ. Impact of hypertension on coronary artery spasm as assessed with intracoronary acetylcholine provocation test. J Hum Hypertens. 2010;24:77-85.


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