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. 1999 Oct;82(4):471–476. doi: 10.1136/hrt.82.4.471

Evidence of partially preserved endothelial dilator function in diseased coronary arteries

D Tousoulis 1, C Tentolouris 1, T Crake 1, C Stefanadis 1, P Toutouzas 1, G Davies 1
PMCID: PMC1760290  PMID: 10490563

Abstract

OBJECTIVE—To examine the effects of substance P (endothelium dependent vasodilator) and glyceryl trinitrate (endothelium independent vasodilator) on epicardial coronary arteries in patients with normal coronary angiograms and patients with coronary artery disease.
DESIGN—Intracoronary infusions of normal saline, the receptor mediated nitric oxide stimulant substance P (5.6 and 27.8 pmol/min each for five minutes), and glyceryl trinitrate (250 µg bolus) were given in 24 patients with coronary artery disease and stable angina, and in nine patients with normal angiograms. The diameter of proximal and distal coronary segments was measured by computerised quantitative angiography
RESULTS—Proximal segments of patients with coronary artery disease dilated less than those of patients with normal angiograms in response to 27.8 pmol/min substance P (mean (SEM): 7.9 (1.3)% v 15 (2.3)% respectively, p < 0.01). The proximal segments of diseased arteries also dilated less than those of "normal" arteries in response to glyceryl trinitrate (10.2 (1.6)% v 18.4 (2.9)%, respectively, p < 0.01). The responses of distal segments to substance P and glyceryl trinitrate were similar in the two patient groups. There were correlations (all p < 0.001) between the coronary diameter after substance P and after glyceryl trinitrate in normal proximal segments (r = 0.94) and normal distal segments (r = 0.64), in diseased proximal segments (r = 0.95) and diseased distal segments (r = 0.89), and for coronary stenoses (r = 0.93).
CONCLUSIONS—Proximal segments of patients with coronary disease dilated less than the proximal segments of "normal" patients in response to substance P and glyceryl trinitrate. The response to substance P is substantial and closely correlated with the response to glyceryl trinitrate in both "normal" patients and those with coronary disease. This suggests that although the proximal segments of diseased coronary arteries have a reduced capacity to dilate in response to direct stimulation of smooth muscle cell relaxation, they retain much of their endothelium dependent vasodilator function.


Keywords: endothelium; nitric oxide; coronary artery disease; glyceryl trinitrate

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Figure 1  .

Figure 1  

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Plot showing mean dose dependent responses (mean coronary luminal diameter with SEM) to substance P (subP) and glyceryl trinitrate (GTN) for proximal and distal segments in patients with coronary artery disease (CAD) and in patients with "normal" coronary arteries (CA). A progressive increase in mean luminal diameter occurred with increasing doses of substances P and glyceryl trinitrate administration. BL, baseline; NS, saline.

Figure 2  .

Figure 2  

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Bar graph showing mean (with SEM) percentage dilatation from saline after intracoronary infusion of 5.6 and 27.8 pmol/min substance P (subP) and after glyceryl trinitrate (GTN) administration for proximal and distal coronary segments in patients with "normal" coronary arteries (CA) and in patients with coronary artery disease (CAD) and in coronary stenoses. In patients with normal coronary arteries, proximal segments showed a significantly greater dilatation (p < 0.01) during substance P and glyceryl trinitrate infusions than in patients with coronary artery disease.

Figure 3  .

Figure 3  

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Scatterplot showing the relation between the coronary diameter in response to glyceryl trinitrate (GTN) and to substance P in proximal and distal segments in patients with "normal" coronary angiograms (NCAs) and in patients with coronary artery disease (CAD) and in coronary stenoses. Linear regression analysis show a significant correlation between these two variables in both groups. The slope of this linear relation between these two variables was close to unity (0.9-1.0).

Figure 4  .

Figure 4  

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Graph showing per cent response to 27.8 pmol/min substance P (SP2) from baseline of the bottom and top quartiles of proximal segments together with the response of their corresponding distal segments in patients with coronary artery disease. The proximal segments of diseased coronary arteries were divided into quartiles according to their response to substance P. The distal segment response to substance P is greater than the proximal segment response in both groups (p < 0.01), but less in the bottom quartile than in the top quartile (*p < 0.05).

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