title: ACE inhibition with spirapril improves diastolic function at rest independent of vasodilation during treatment with spirapril in mild to moderate hypertension.
abstract: The effects of the ACE inhibitor spirapril and of hydrochlorothiazide on left ventricular diastolic function were studied. Thirteen patients with mild to moderate essential hypertension completed this randomized, double-blinded, placebo-controlled, crossover study. After a three-week run-in period the patients entered three periods lasting four weeks each, wherein they were treated with placebo, spirapril, or hydrochlorothiazide. Blood pressure, hemodynamic variables (stroke volume, heart rate, cardiac output, index of contractility, and systemic vascular resistance), echocardiography (left ventricular mass), and Doppler-derived atrial to early (A/E)-ratio velocity time integrals (VTI) were measured at the end of each of the four periods. Spirapril lowered the A/E-ratio VTIs (0.57, 0.12-1.00) (P < 0.02) as compared with both placebo (0.80, 0.50-2.67) and hydrochlorothiazide (0.83, 0.44-1.25), and the drug normalized the A/E-ratio VTI in those patients with elevated values. The hemodynamic variables, left ventricular mass, and end-systolic wall stress were unchanged during all three treatments. There were no significant changes in mean blood pressure during the treatment periods. These results indicate that spirapril lowers A/E ratio within four weeks in patients with mild to moderate essential hypertension. It thereby seems able to improve left ventricular diastolic function. The effect is not dependent upon changes in hemodynamic variables, blood pressure, left ventricular mass, or end-systolic wall stress.
authors.affiliation: Department of Clinical Physiology, Frederiksberg Hospital, Frederiksberg, Denmark.
authors.forename: J R
authors.initials: JR
authors.lastname: Petersen
authors.forename: H
authors.initials: H
authors.lastname: Drabaek
authors.forename: G
authors.initials: G
authors.lastname: Gleerup
authors.forename: J
authors.initials: J
authors.lastname: Mehlsen
authors.forename: L J
authors.initials: LJ
authors.lastname: Petersen
authors.forename: K
authors.initials: K
authors.lastname: Winther
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002307:Cardiography, Impedance / Q000187:drug effects; D018592:Cross-Over Studies; D003971:Diastole / Q000187:drug effects*; D004311:Double-Blind Method; D004452:Echocardiography / Q000187:drug effects; D004656:Enalapril / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D012146:Rest; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D004656:Enalapril; C052555:spirapril