Long-term cardiac effects of hypotensive agents in normotensive mature rats: comparison of beta-blocking agent and converting enzyme inhibition.
The hemodynamic and myocardial effects of chronic treatment (5 months) with converting enzyme inhibitor (CEI, enalapril, group T1, n = 10) or a beta 1 blocker (atenolol, group T2, n = 13) of normotensive mature male Wistar rats were studied and compared to untreated younger rats (group C0, 11 months old, n = 14) and to untreated age-matched controls (group C1, 16 months old, n = 14). Heart rate was significantly decreased in T2 rats but unchanged in the T1 group. There was a significant decrease in systolic and diastolic arterial blood pressure (BP) in both treated groups (systolic T1:90 +/- 17, T2: 87 +/- 10, vs. C1: 102 +/- 11 mm Hg, and diastolic T1: 60 +/- 17, T2: 59 +/- 9, vs. C1: 73 +/- 13 mm Hg). Cardiac output was unchanged by therapy but stroke volume was significantly increased in the T2 group (0.24 +/- 0.03 vs. 0.19 +/- 0.04 cm3 in C1). Total peripheral resistance was significantly decreased in T1 and T2 groups. Left ventricular weight to body weight ratio (LVW/BW) was significantly decreased in T1 (1.74 +/- 0.11 vs. 2.02 +/- 0.22 in C1) but unchanged in T2 (1.90 +/- 0.15 vs. 2.02 +/- 0.22). The left ventricular passive pressure-volume curve was significantly rightward shifted by beta-blocker therapy (T2) but unchanged by CEI (T1). This corresponds to a decrease of chamber stiffness k in the T2 group compared to C1 and T1 groups. A significant fibrosis was seen in group T2 (mean collagen fiber thickness of 3.03 +/- 0.24 vs. 2.8 +/- 0.15 micron) but not in the T1 group (2.94 +/- 0.14 vs. 2.8 +/- 0.15 micron). Thus, despite the similar decrease in BP induced by the CEI and the beta blocker, the cardiac effects of the two drugs were opposite: CEI decreased LVW/BW with no change in the left ventricular pressure-volume curve and myocardial fibrosis whereas beta blocker did not change the LVW/BW, but induced a left ventricular dilation associated with a decrease in chamber stiffness and an increase in subendocardial fibrosis.
Azizi
M
M
INSERM U36, Hôpital Broussais, Paris, France.
Levy
B
B
Salzmann
J L
JL
Cerol
M L
ML
Poitevin
P
P
Ménard
J
J
Michel
J B
JB
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D007457:Iodine Radioisotopes; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009218:Myosins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007457:Iodine Radioisotopes; D007527:Isoenzymes; D003094:Collagen; D009218:Myosins