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 LI)-induced hyper tension and structural vascular changes and the effect of dietary sodi um supplementation on these relationships were investigated. Male Spra gue-Dawley rats were treated with 50, 100, or 200 ng.kg(-1).min(-1) An g 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 d iet (7% NaCl). Additional rats were sham-operated and fed normal sodiu m (control rats) or high sodium diet. Plasma Ang II level of rats rece iving 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 interm ediate-size (100 to 150 mu m OD) resistance arteries were measured in maximally dilated, pump-perfused (55 to 60 mm Hg), in situ fixed mesen teric vascular beds of rats, and wall-to-lumen ratios (W/L) were calcu lated. Large mesenteric arteries of rats treated with 100 ng.kg(-1).mi n(-1) Ang II for 12 weeks were examined to distinguish hypertrophy fro m hyperplasia of vascular muscle. Tail systolic blood pressure (BP) an d W/L of resistance arteries of Ang II-treated rats increased in a dos e-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 i n 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<0.0 1) and W/L of small resistance arteries by 28% (P<0.01) (synergism). I n rats treated with 100 ng.kg(-1).min(-1) Ang II for 12 weeks, arteria l smooth muscle cell thickness was increased without a change in the n umber of cell layers (hypertrophy). There was a dissociation between t he average BP load (the area under the weekly systolic BP curve) of An g 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 sup plementation Dissociation between BP and vascular structure in Ang II- treated rats suggests that a direct trophic effect of Ang II may contr ibute to the development of structural vascular changes.