The dose and time dependence of angiotensin II: (Ang LI)-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 (7% 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=25) in central rats (P<0.03), Lumen and external diameters of small (50 to 100 mu m OD) and intermediate-size (100 to 150 mu m 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.
