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 <or= 0.001). Furthermore, TOP significantly increased antioxidants like superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione and decreased lipid peroxidation product malondialdehyde significantly. Furthermore, TOP scavenges more free radicals than captopril in pyrogallol auto-oxidation and deoxyribose method. Unlike free sulfur of captopril, thiophene ring may act as a free radical scavenger besides chelating the Zn present in the active site of ACE.
Hanif
Kashif
K
Peptide Synthesis Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi, India.
Snehlata
Pavar
Mahesh C
MC
Arif
Ehtesham
E
Biswas
Parbati
P
Fahim
Mohammad
M
Pasha
M A Qadar
MA
Pasha
Santosh
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D013876:Thiophenes / Q000494:pharmacology*
C540584:3-thienylalanyl-ornithyl-proline; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D016166:Free Radical Scavengers; D009842:Oligopeptides; D013876:Thiophenes