ABSTRACT
The spontaneously hypertensive stroke-prone (SHRSP) rat is a commonly used model of cerebrovascular disease and hypertension. SHRSP rats have been shown to develop stroke-related symptoms (SRS) by age 14 weeks when fed a purified diet, such as AIN-93G, supplemented with 1% NaCl. We conducted a pathology pilot study to compare the incidence of SRS in SHRSP rats fed either AIN-93G (with 1% NaCl in drinking water) or commercially available rat chow (with 4% NaCl in the diet), starting at 8 weeks of age. These results prompted us to analyze data from 5 earlier feeding trials using SHRSP rats. Overall, we found that SHRSP rats fed AIN-93G purified diet for 8 or 17 weeks did not demonstrate SRS (n = 18), whereas all SHRSP rats fed lab chow exhibited SRS at age 15.1 ± 0.6 weeks (n = 23). In addition, SHRSP rats fed lab chow had decreased mass gain starting at age 13 weeks, as well as decreased feed efficiencies after the first 5 weeks of feeding (p < 0.05). In conclusion, our data suggest that diet composition is a major contributor to the onset of stroke in SHRSP rats and that diet choice should be critically evaluated based on endpoint measures in the SHRSP model.
Subject(s)
Animal Feed/adverse effects , Diet/adverse effects , Hypertension/complications , Stroke/etiology , Age Factors , Aging , Animals , Blood Pressure , Disease Models, Animal , Eating , Endpoint Determination , Hypertension/physiopathology , Male , Rats , Rats, Inbred SHR , Rats, Wistar , Risk Factors , Stroke/physiopathology , Weight GainABSTRACT
Oxidative stress in the vasculature and kidneys contributes to hypertension, a major risk factor for cardiovascular disease. Blueberries (BB) are rich in antioxidants, and so we hypothesized that feeding diets enriched with BB would slow the development of hypertension in spontaneously hypertensive stroke-prone rats (SHRSP). Eight-week-old normotensive rats and SHRSP were fed either a control diet (Con) or a diet enriched with 3% freeze-dried BB for 8 weeks. Systolic blood pressure (SBP) was measured at weeks 2, 4, 6, 7, and 8 by the tail cuff method, and urine was collected at weeks 4 and 8. The SBP was elevated in SHRSP relative to normotensive rats over the entire 8-week feeding period. In SHRSP consuming BB, SBP was 19% lower at week 4 and 30% lower at week 6, relative to SHRSP on Con. Maximum SBP was 216 +/- 11 mm Hg in SHRSP consuming Con vs 178 +/- 15 mm Hg in the BB-fed group (P = .036). Spontaneously hypertensive stroke-prone rats had elevated levels of urine F2-isoprostanes/creatinine relative to normotensive rats, indicating systemic oxidative stress in this strain. Blueberry feeding had no effect on urinary excretion of F2-isoprostanes; therefore, it is unlikely that a systemic antioxidant effect of BB is responsible for the antihypertensive effects at weeks 4 and 6. Blueberry-fed rats had reduced markers of renal oxidative stress, such as proteinuria and kidney nitrites. Thus, a 3% BB diet may be capable of protecting the kidneys from oxidative damage in SHRSP, thereby reducing the magnitude of hypertension.
