Relationship between angiotensin II (ANGII), oxidative stress (OXST), and mean arterial pressure (MAP) in the spontaneously hypertensive rat (SHR), effects of chronic captopril (CAP) treatment

Abstract

It has been reported that increases in MAP found in the SHR coexists with high levels of AngII, while plasma renin activity (PRA) remains normal. It has also been shown that AngII not only acts as a potent vasoconstrictor, but also can increase the production of superoxide ions leading to lipid peroxidation and OXST. This suggests chronic treatment of the SHR with the ACE inhibitor CAP, will not only reduce MAP, but also reduce circulating levels of AngII and OXST as measured through the production of TBARS. Four groups of SHR rats 12 weeks old were used for this study. Two groups were chronically treated with CAP (100 mg/kg/day) in their drinking water for 16 days, while the other two groups served as untreated time controls. One of each of these groups was anesthetized (n=5 for each group) for measurement of MAP and collection of blood samples for measurements of AngII, PRA and TBARS while the remaining groups underwent the same procedures after decapitation (n=3 for each group) to eliminate the effects of anesthesia. In the CAP treated SHR, MAP was significantly (p<0.05) reduced from (160.4±5.15 to 92.0±4.56 mmHg) when compared to the SHR untreated controls. Measurements of AngII and TBARS were also significantly reduced with CAP treatment from 52.3 ± 6.0 to 23.7±2.2 pg/ml, and from 4.20±0.03 to 2.40±0.10 nmol/ml respectively when compared to the control group, while levels of PRA were significantly increased from (9.20±1.50 to 36.70±7.80 ng/ml/hr) with CAP treatment. Anesthesia significantly increased the measurements of both AngII and PRA in both groups AngII (control group 52.3 ±6.0 to 836±205 pg/ml, CAP treated 23.7 ±2.2 to 630±47 pg/ml) PRA (control group 9.2 ±1.5 to 26.4±6.6 ng/ml/hr, CAP treated 36.7 ±7.8 to 42.0±1.5 ng/ml/hr). In summary 1) CAP treatment significantly reduces MAP along with plasma levels of AngII and TBARS, while PRA levels are significantly increased. 2) Anesthesia falsely increases AngII and PRA measurements to a point where changes in physiological levels are not evident. Conclusion. Reductions in MAP mediated through CAP treatment of the SHR coincides with reductions in both plasma AngII and TBARS, a marker of OXST. Therefore, it can be concluded that AngII and OXST may play a significant role in the onset of hypertension in the SHR.