title: Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Ga. 30303.
authors.forename: C B
authors.initials: CB
authors.lastname: Treasure
authors.forename: J L
authors.initials: JL
authors.lastname: Klein
authors.forename: J A
authors.initials: JA
authors.lastname: Vita
authors.forename: S V
authors.initials: SV
authors.lastname: Manoukian
authors.forename: G H
authors.initials: GH
authors.lastname: Renwick
authors.forename: A P
authors.initials: AP
authors.lastname: Selwyn
authors.forename: P
authors.initials: P
authors.lastname: Ganz
authors.forename: R W
authors.initials: RW
authors.lastname: Alexander
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000328:Adult; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D014655:Vascular Resistance; D014664:Vasodilation
chemical_list: D000241:Adenosine; D000109:Acetylcholine