Endothelium-dependent dilator response to substance P in patients with coronary spastic angina

Division of Cardiology, Kumamoto University School of Medicine, Japan.

OBJECTIVE. This study was designed to examine whether patients with coronary spastic angina have an impaired coronary artery dilator response to substance P, an endothelium-dependent vasodilator. BACKGROUND. Impairment of the endothelium-dependent vasodilator response has been suggested to be involved in the pathogenesis of coronary spasm. METHODS. In 11 patients with coronary spastic angina and 11 control patients, substance P was infused into the coronary artery at 20 pmol/min for 5 min. Incremental doses of acetylcholine were then injected into the coronary artery. The effects of these drugs and nitroglycerin on the coronary artery diameter were quantitatively analyzed. RESULTS. Heart rate, systolic blood pressure and rate-pressure product did not change after substance P infusion. In 12 coronary arteries of the patients with coronary spastic angina, spasm was induced with acetylcholine. At the site of coronary spasm documented, the lumen diameter, which was 1.6 +/- 0.5 mm at baseline, increased to 2.1 +/- 0.7 mm after substance P infusion (p less than 0.01). It decreased to 0.2 +/- 0.3 mm during acetylcholine-induced spasm (p less than 0.001) and increased to 2.3 +/- 0.8 mm after nitroglycerin administration (p less than 0.001 vs. baseline and p = NS vs. after substance P infusion). Of the 12 arteries with spasm, 5 were angiographically normal and the other 7 were minimally or moderately atherosclerotic: the diameter change after substance P was +28 +/- 20% and +30 +/- 22%, respectively (p = NS). In control patients, the diameter of the middle portion of the left anterior descending artery, which was 2.0 +/- 0.4 mm at baseline, increased to 2.5 +/- 0.4 mm after substance P infusion (p less than 0.001). The diameter changes after substance P infusion were not different between the patients with coronary spastic angina and control patients. CONCLUSIONS. Substance P dilated the artery with spasm of the patients with coronary spastic angina to a degree similar to that in control patients, indicating the preserved endothelium-dependent dilator response at the site of coronary spasm by way of substance P receptor.

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