Left ventricular diastolic function during adrenergic stress in essential hypertension: acute and chronic effects of ACE inhibition.
We studied the changes in left ventricular (LV) diastolic function induced by angiotensin-converting enzyme (ACE) inhibition at rest and during adrenergic stimulation and their relation to blood pressure (BP) variations to determine whether reductions in the renin-angiotensin system may improve diastolic function irrespective of BP reduction. Echocardiographic indices of systolic and diastolic function, plasma catecholamines as estimated by high-pressure liquid chromatography, and BP variations (Dynamap) were determined at rest and during the cold pressor test (CPT) before and 6 hours and 20 days after ACE inhibition (lisinopril), 20 mg/day by mouth in 10 subjects with uncomplicated essential hypertension. Blood Pressure was significantly reduced after both 6 hours and 20 days of therapy. The cold pressor test induced similar increases in BP in both basal conditions and after acute and chronic treatment. Catecholamine levels were unchanged by the therapy. Systolic function, evaluated by fractional shortening, ejection fraction, and systolic dV/dt, was normal and unchanged during CPT and after treatment. Diastolic function, assessed by volume curve analysis, showed a reduced percentage contribution of rapid filling to total diastolic filling, an increase in the contribution of the atrial systole, and an increase in the isovolumetric relaxation time. During CPT these parameters deteriorated further in response to increased afterload. Lisinopril therapy induced significant increases in end-diastolic volume (p < 0.005) with a progressive increase in the rapid filling dV/dt (p < 0.005 at rest; p < 0.001 during CPT) and a reduction in isovolumetric relaxation (p < 0.0001 at rest and p < 0.01 during CPT). The correlation between systolic BP (afterload) and the rapid filling dV/dt, both at rest and during CPT, was modified by treatment with the ACE inhibitor, with significantly higher rapid filling dV/dt values, and with the pressure loads equal (reduction of the slope and rightward shift of the correlation line). The improvement in diastolic function achieved by ACE inhibition at rest and during CPT appears unrelated to plasma catecholamines and only partly ascribable to the reduced pressure load. The tissue angiotensin II reduction might by itself improve the myocardial response to the pressure load and adrenergic stimulation.
Covi
G
G
Istituto di Clinica Medica, Cattedra di Medicina Interna, Verona, Italy.
Sheiban
I
I
Gelmini
G
G
Arcaro
G
G
Tonni
S
S
Bolner
A
A
Piemonte
G
G
Lechi
A
A
D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003080:Cold Temperature; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D016014:Linear Models; D017706:Lisinopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002395:Catecholamines; D000804:Angiotensin II; D017706:Lisinopril