(Hypertension. 1996;27:1115-1120.)
© 1996 American Heart Association, Inc.
Articles |
Preweanling Administration of Terazosin Decreases Blood Pressure of Hypertensive Rats in Adulthood
From the Department of Psychology, University of Virginia, Charlottesville.
Correspondence to Richard McCarty, PhD, Department of Psychology, 102 Gilmer Hall, University of Virginia, Charlottesville, VA 22903-2477. E-mail rcm@virginia.edu.
Abstract To examine the contribution of the sympathetic
nervous system to the development of hypertension, we injected
spontaneously hypertensive rat (SHR) pups and normotensive Wistar-Kyoto
rat (WKY) pups twice daily with saline (1.0 mL/kg SC) or terazosin (0.5
mg/kg SC), an 
1-adrenoceptor antagonist,
from postnatal day 1 through 21. We determined the effectiveness and
duration of action of this terazosin dose in pilot studies with adult
SHR and WKY. Body weights of WKY pups were greater than body weights of
SHR pups from postnatal day 1 through 21. In addition, body weights of
terazosin-treated pups of both strains were comparable to
body weights of saline-injected littermate controls. Indirectly
measured systolic pressures of terazosin-treated SHR were
reduced significantly at 60 and 90 days of age but not at 30 days of
age compared with saline-injected littermate controls. Terazosin
did not affect systolic pressures of WKY, measured at 30, 60,
and 90 days of age. At 100 days of age, in chronically catheterized
rats, mean arterial pressures of terazosin-treated SHR
were reduced significantly compared with those of saline-injected
littermate controls. In contrast, terazosin did not affect mean
arterial pressures of WKY at 100 days of age. Finally,
preweanling treatment with terazosin did not alter patterns of open
field behavior of adult SHR or WKY. SHR were significantly more active
and reared more frequently compared with WKY. These findings indicate
that the time between birth and weaning at 21 days of age is critical
for the full expression of the hypertensive phenotype in SHR.
Chronic blockade of 1-adrenoceptors during the
preweanling period in SHR may reduce vascular hypertrophy,
leading to long-term reductions in arterial pressure.
Key Words: rats, inbred SHR • nervous system, sympathetic • development • muscle, smooth, vascular • adrenergic receptors • phenotype
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