From the Department of Medicine, VA Medical Center, and the University of
Minnesota (Minneapolis).
Correspondence to Geza Simon, MD, Hypertension Clinic, VA Medical Center, Minneapolis, MN 55417.
Abstract—The dose and time
dependence of angiotensin II (Ang II)–induced hypertension
and structural vascular changes and the effect of dietary sodium
supplementation on these relationships were investigated. Male
Sprague-Dawley rats were treated with 50, 100, or 200 ng ·
kg-1 · min-1 Ang II subcutaneously for
4 or 12 weeks on normal sodium diet (0.7% NaCl) or with 50 ng ·
kg-1 · min-1 Ang II SC for 12 weeks on
high sodium diet (2% NaCl). Additional rats were sham-operated and fed
normal sodium (control rats) or high sodium diet. Plasma Ang II level
of rats receiving 100 ng · kg-1 ·
min-1 Ang II for 4 weeks was 26±5 pg/mL (mean±SEM, n=7)
compared with 11±2 pg/mL (n=15) in control rats
(P<0.03). Lumen and external diameters of small (50 to
100 µm OD) and intermediate-size (100 to 150 µm OD)
resistance arteries were measured in maximally dilated, pump-perfused
(55 to 60 mm Hg), in situ fixed mesenteric vascular beds of rats,
and wall-to-lumen ratios (W/L) were calculated. Large mesenteric
arteries of rats treated with 100 ng · kg-1
· min-1 Ang II for 12 weeks were examined to distinguish
hypertrophy from hyperplasia of vascular muscle. Tail
systolic blood pressure (BP) and W/L of resistance arteries of
Ang II–treated rats increased in a dose-dependent manner. Treatment
with 50 ng · kg-1 · min-1 Ang
II for 12 weeks had no significant effect on BP but produced the same
increase in W/L (+10%, n=8, P<0.06) as 100 ng ·
kg-1 · min-1 Ang II for 4 weeks (+9%,
n=18, P<0.05) (time dependence). A 2% NaCl diet for 12
weeks had no significant effect on either BP or W/L, but in combination
with 50 ng · kg-1 · min-1 Ang
II, it increased systolic BP by 31 mm Hg
(P<0.01) and W/L of small resistance arteries by 28%
(P<0.01) (synergism). In rats treated with 100 ng
· kg-1 · min-1 Ang II for 12 weeks,
arterial smooth muscle cell thickness was increased without
a change in the number of cell layers (hypertrophy). There
was a dissociation between the average BP load (the area under the
weekly systolic BP curve) of Ang II–treated rats and the W/L
of their mesenteric resistance arteries. Ang II–induced hypertension
and structural vascular changes are dose- and time-dependent and
synergistically enhanced by dietary sodium supplementation.
Dissociation between BP and vascular structure in Ang II–treated rats
suggests that a direct trophic effect of Ang II may contribute to the
development of structural vascular changes.
© 1998 American Heart Association, Inc.
Scientific Contributions
Structural Vascular Changes in Hypertension
Role of Angiotensin II, Dietary Sodium Supplementation, Blood Pressure, and Time
Key Words: arteries • morphometry • mesenteric circulation
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