Effect of 3-thienylalanine-ornithine-proline, new sulfur-containing angiotensin-converting enzyme inhibitor on blood pressure and oxidative stress in spontaneously hypertensive rats.

Sulfur-containing angiotensin-converting enzyme (ACE) inhibitors have an edge over other inhibitors in improving endothelial dysfunction and reducing oxidative stress. In this study, effect of new sulfur-containing ACE inhibitor, 3-thienylalanine-ornithine-proline (TOP), was studied on blood pressure (BP) and oxidative stress in Spontaneously Hypertensive Rats (SHRs). Acute oral administration of 5 mg/kg of TOP significantly lowered systolic blood pressure for longer periods (18 +/- 0.5 hours, P < 0.05 vs. 16 +/- 0.5 hours) than captopril (20 mg/kg). Thiophene ring of TOP is devoid of free sulfur and may avoid early oxidation resulting in longer duration of action. Chronic oral administration of TOP (5 mg/kg twice a day) for 7 days lowered BP from 189.1 +/- 2.5 to 161.7 +/- 2.6 mm Hg (P < 0.05), decreased the ACE activity, and increased the nitrite levels in various tissues (P < 0.05) and serum (P