TY - JOUR
T1 - Hemodynamic effects of renin inhibition by enalkiren in chronic congestive heart failure
AU - Neuberg, Gerald W.
AU - Kukin, Marrick L.
AU - Penn, Joshua
AU - Medina, Norma
AU - Yushak, Madeline
AU - Packer, Milton
N1 - Funding Information:
From the Center for Heart Failure Research,D ivision of Cardiology, Department of Medicine, Mount Sinai School of Medicine, The City University of New York, New York, New York. This study was supported in part by Grants ROl-HL-25055 and K04-HL-01229 from the National Heart, Lung, and Blood Institute, Bethesda,M aryland, and by a grant from Abbott Laboratories, Abbott Park, Illinois. Dr. Packer is the recipient of a Research Career Development Award from the National Institutes of Health, Bethesda, Maryland. Manuscript received June 11,1990, revised manuscript receiveda nd acceptedA ugust 30, 1990.
PY - 1991/1/1
Y1 - 1991/1/1
N2 - Previous efforts to block the renin-angiotensin system in patients with chronic congestive heart failure (CHF) have focused on 2 distal sites in the system, the angiotensin-converting enzyme and the angiotensin II receptor. Recent work, however, has led to the development of agents that directly inhibit renin, the proximal step in the cascade. In this study, we investigated the hemodynamic effects of renin Inhibition In 9 patients with chronic CHF by using enalkiren, a primate-selective, dipeptide renin inhibitor, which has been previously shown to suppress plasma renin activity and to lower blood pressure in hypertensive patients. The acute intravenous administration of enalkiren (1.0 mg/kg) produced increases in cardiac index (2.0 ± 0.3 to 2.3 ± 0.1 liter/min/m2) and stroke volume index (26 ± 3 to 34 ± 4 ml/m2) and decreases in left ventricular filling pressure (31 ± 3 to 25 ± 3 mm Hg), mean right atrial pressure (15 ± 1 to 13 ± 2 mm Hg), heart rate (78 ± 5 to 72 ± 6 beats/min) and systemic vascular resistance (2,199 ± 594 to 1,339 ± 230 dynes·s·cm-5) (all p < 0.01 to 0.05). These observations indicate that renin inhibition produces hemodynamic benefits in patients with chronic CHF and could potentially provide a novel approach to interfering with the renin-angiotensin system in patients with this disorder.
AB - Previous efforts to block the renin-angiotensin system in patients with chronic congestive heart failure (CHF) have focused on 2 distal sites in the system, the angiotensin-converting enzyme and the angiotensin II receptor. Recent work, however, has led to the development of agents that directly inhibit renin, the proximal step in the cascade. In this study, we investigated the hemodynamic effects of renin Inhibition In 9 patients with chronic CHF by using enalkiren, a primate-selective, dipeptide renin inhibitor, which has been previously shown to suppress plasma renin activity and to lower blood pressure in hypertensive patients. The acute intravenous administration of enalkiren (1.0 mg/kg) produced increases in cardiac index (2.0 ± 0.3 to 2.3 ± 0.1 liter/min/m2) and stroke volume index (26 ± 3 to 34 ± 4 ml/m2) and decreases in left ventricular filling pressure (31 ± 3 to 25 ± 3 mm Hg), mean right atrial pressure (15 ± 1 to 13 ± 2 mm Hg), heart rate (78 ± 5 to 72 ± 6 beats/min) and systemic vascular resistance (2,199 ± 594 to 1,339 ± 230 dynes·s·cm-5) (all p < 0.01 to 0.05). These observations indicate that renin inhibition produces hemodynamic benefits in patients with chronic CHF and could potentially provide a novel approach to interfering with the renin-angiotensin system in patients with this disorder.
UR - http://www.scopus.com/inward/record.url?scp=0025959255&partnerID=8YFLogxK
U2 - 10.1016/0002-9149(91)90101-P
DO - 10.1016/0002-9149(91)90101-P
M3 - Article
C2 - 1986506
AN - SCOPUS:0025959255
SN - 0002-9149
VL - 67
SP - 63
EP - 66
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 1
ER -