Structural vascular changes in hypertension: role of angiotensin II, dietary sodium supplementation, blood pressure, and time.
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 microm OD) and intermediate-size (100 to 150 microm 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.
Department of Medicine, VA Medical Center, and the University of Minnesota, Minneapolis, USA.
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Simon
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Illyes
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Csiky
D000704:Analysis of Variance; D000804:Angiotensin II / Q000009:adverse effects / Q000097:blood / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects; D013997:Time Factors
D012982:Sodium, Dietary; D000804:Angiotensin II