Circulation, Vol 87, 86-93, Copyright © 1993 by American Heart Association
CB Treasure, JL Klein, JA Vita, SV Manoukian, GH Renwick, AP Selwyn, P Ganz and RW Alexander
BACKGROUND. Patients with hypertension and myocardial hypertrophy may have
signs and symptoms of myocardial ischemia in the absence of obstructive
coronary disease. Prior investigations have demonstrated impaired coronary
flow reserve and have led to speculation that microvascular dysfunction
might contribute to ischemia in these patients. Experimental studies have
shown that the endothelium, an important regulator of microvascular tone,
can be damaged by hypertension and is dysfunctional in cardiomyopathy. We
hypothesized that endothelium-dependent vasodilation is impaired in the
coronary microvasculature of patients with hypertension and ventricular
hypertrophy. METHODS AND RESULTS. We studied coronary microvascular
responses in 10 patients with left ventricular hypertrophy secondary to
essential hypertension (HTN) (mean arterial pressure at catheterization,
151/94 mm Hg; mean posterior wall thickness, 1.4 +/- 0.1 cm) and nine
normal control subjects with no history of hypertension (mean arterial
pressure at catheterization, 128/75 mm Hg; mean posterior wall thickness,
1.0 +/- 0.02 cm) using the intracoronary Doppler catheter and quantitative
angiography to assess changes in coronary blood flow (CBF). All patients
had normal left ventricular systolic function. To assess microvascular
endothelial function, we infused the endothelium-dependent vasodilator
acetylcholine (10(-8)-10(- 6) M) and the endothelium-independent
vasodilator adenosine (10(-6)-10(- 4) M) into the left anterior descending
coronary artery. In response to acetylcholine, CBF increased only 32 +/-
25% in HTN patients, whereas CBF increased 192 +/- 39% in normal control
subjects (p = 0.003). CBF increased 465 +/- 93% in HTN patients and 439 +/-
41% in normal control subjects in response to adenosine (p = NS). The
proportion of coronary flow reserve attributable to endothelium-dependent
dilation (obtained from peak acetylcholine/peak adenosine flow response)
was 48 +/- 9% in normal control subjects but only 7 +/- 8% in HTN patients
(p = 0.008). CONCLUSIONS. Endothelium-dependent vasodilation is markedly
impaired in the coronary microvessels of patients with hypertension and
ventricular hypertrophy. Loss of this vasodilator mechanism may contribute
to disordered coronary flow regulation and the ischemic manifestations of
hypertensive heart disease.
ARTICLES
Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels
Department of Medicine, Emory University School of Medicine, Atlanta, Ga. 30303.
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