Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressor test.

Abstract

Increased vascular constriction has been observed at the site of atherosclerotic lesions, suggesting an association between atherosclerosis and altered vascular tone. While atherosclerosis may increase sensitivity to exogenous vasoconstrictors, little is known about the response of normal and atherosclerotic coronary arteries to an exogenous stimulus that excites the sympathetic nervous system. Therefore, we studied the response to cold pressor test (CPT) using quantitative angiography and Doppler flow velocity measurements in eight patients with angiographically normal coronary arteries (group I), nine patients with mild coronary atherosclerosis (< 50% diameter narrowing) (group II), and 13 patients with advanced coronary stenoses (> 50% diameter narrowing) (group III). In 31 segments of angiographically smooth arteries in group I, the CPT produced vasodilation from a control mean diameter of 2.68 ± 0.09 (mean ± SE) to 2.99 ± 0.09 mm at peak CPT (p < 0.001), a 12 + 1 % increase in diameter. In group II, 27 irregular segments constricted to peak CPT from a mean control diameter of 1.82 ± 0.12 to 1.66 ± 0.12 mm (p < .001), a 9 ± 1% decrease, while 10 smooth segments dilated from a mean control diameter of 1.98 ± 0.11 mm to 2.34 ± 0.15 mm (p < .01), a 19 + 2% increase in diameter. Likewise, in group III, the 17 stenotic segments constricted from 1.16 ± 0.09 to 0.89 ± 0.09 mm (p < .001), a 24 6% decrease; the irregular segments also constricted from 2.44 0.11 to 2.22 0.12 mm (p = .002), a 10 ± 2% decrease. In contrast, two smooth segments dilated from 2.98 to 3.23 mm (mean), an 8% increase in diameter. Coronary blood flow increased 65 ± 4% (mean) during CPT in group I, it increased 15 ± 6% in group II, and it decreased 39 ± 8% in group III. The vasodilator response in four normal patients was partly inhibited by the administration of intracoronary propranolol (17 + 3% increase during control, 10 + 2% increase after propranolol, 41% less dilation; p = .002). We conclude that the response of normal coronary arteries to the CPT test is dilation, in part related to /3-adrenoreceptor stimulation and possibly flow-mediated endothelial dilation or a2-adrenergic activity. The paradoxical vasoconstrictor response induced by atherosclerosis may represent altered catecholamine sensitivity and/or a defect in endothelial vasodilator function. The presence of atherosclerosis impairs vasodilator responses and thus may contribute to the pathogenesis of myocardial ischemia.

Therapeutic Potential of Phosphodiesterase 5 Inhibition for Cardiovascular Disease

“…With dysfunctional endothelium, the release of nitric oxide by the endothelium is significantly compromised, which can result in abnormal vasomotion during exercise, pacing, or exposure to cold. 44 Application of acetylcholine-in healthy arteries a powerful vasodilator because of the release of nitric oxide from the endothelium-can lead to paradoxical vasoconstriction, as constrictor effects of muscarinic receptors on vascular smooth muscles predominate over endothelial nitric oxide release. 45 The study by Halcox et al 43 demonstrated that especially coronary arterial segments that contracted after application of acetylcholine, denoting endothelial dysfunction, dilated after application of acetylcholine combined with sildenafil treatment, suggesting that the inhibition of cGMP breakdown by sildenafil could at least in part compensate for reduced nitric oxide-related cGMP production due to endothelial dysfunction.…”

George Lyman Duff Memorial Lecture. Arterial imaging and atherosclerosis reversal.

“…Elevated LDL-C reduces dilation that normally occurs, 36 and visible lesions reduce or even reverse dilation. 37 Vascular remodeling and chronic EDRF effects, which appear closely related to lesion progression and regression, have been observed in several lipid-lowering trials. Early indication of lesion remodeling came from the Lifestyle Heart Trial, in which favorable changes in the entrance and exit shape of lesions were reported in the intensively treated group.…”

Change of Coronary Flow Velocity During the Cold Pressor Test Is Related to Endothelial Markers in Subjects With Chest Pain and a Normal Coronary Angiogram

“…These changes result in an increase of coronary blood flow and dilation of coronary arteries. 18 On the contrary, CPT can induce blunt vasodilatation or paradoxical vasoconstriction in patients with coronary endothelial dysfunction. 18 The vasomotor dysfunction to CPT is observed very early in the development of atherosclerosis.…”

“…18 On the contrary, CPT can induce blunt vasodilatation or paradoxical vasoconstriction in patients with coronary endothelial dysfunction. 18 The vasomotor dysfunction to CPT is observed very early in the development of atherosclerosis. 19 However, it is not completely defined that change of coronary flow velocity of the distal LAD during CPT with TTE is related to actual coronary endothelial function.…”