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From the Department of Medical Sciences, University of Brescia, Brescia,
Italy; and the Department of Pharmacology, University of Aarhus, Aarhus,
Denmark (M.J.M.).
Correspondence to Damiano Rizzoni, MD, Cattedra di Semeiotica e Metodologia Medica, Scienze Mediche, University of Brescia, c/o 1a Medicina, Spedali Civili, 25100 Brescia, Italy. E-mail Damiano.Rizzoni{at}schering-plough.it
Abstract—We evaluated the effects on
cardiovascular structure of the
angiotensin-converting enzyme (ACE) inhibitor
enalapril and of the angiotensin II receptor blocker
losartan, administered either at hypotensive or nonhypotensive
dosage in spontaneously hypertensive rats (SHR). SHR were treated from
ages 4 to 12 weeks with low-dose (1 mg · kg-1
· d-1) enalapril, low-dose (0.5 mg ·
kg-1 · d-1) losartan,
high-dose (25 mg · kg-1 · d-1)
enalapril, or high-dose (15 mg · kg-1 ·
d-1) losartan. Untreated WKY and SHR were also
studied. Rats were killed at 13 weeks of age, and the heart was
weighed. Mesenteric small arteries were dissected and mounted on a
micromyograph for determination of media thickness and lumen diameter.
In fixed arteries, cell volume, number of cells per segment length, and
number of cell layers were measured using the unbiased "disector"
method. Systolic blood pressure was significantly reduced by
the high doses of both drugs, but the hypotensive effect was greater
with enalapril than with losartan (P<0.05). In
the high-dose enalapril and losartan groups, there were similar
reductions in relative left ventricular mass, media/lumen
ratio, and number of cell layers of resistance arteries; however, there
were no differences in the cell volume or number of cells per segment
length of resistance arteries. Low-dose enalapril did not affect
systolic blood pressure or any of the structural
parameters. The results show that the hypotensive effects
of both losartan and enalapril were associated with outward
remodeling of resistance arteries at the cellular level. The effect of
losartan on resistance artery structure was equal to that of
enalapril, despite the smaller hypotensive effect.
© 1998 American Heart Association, Inc.
Scientific Contributions
Effects of Losartan and Enalapril on Small Artery Structure in Hypertensive Rats
Key Words: losartan • enalapril • hypertrophy • angiotensin-converting enzyme inhibitors • angiotensin II • vascular resistance
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