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Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0b013e318280e16e
Original Article

Sulfur-Containing Angiotensin-Converting Enzyme Inhibitor 3-Thienylalanine-Ornithyl-Proline Activates Endothelial Function and Expression of Genes Involved in Renin–Angiotensin System

Chaudhary, Snehlata PhD*,†; Seth, Mahesh Kumar MSc*,§; Vats, Ishwar Dutt PhD*; Kumar, Krishan MPhil*; Biswas, Parbati PhD; Karar, Jayashree PhD; Hussain, M. Ejaz PhD§; Pasha, M.A.Q. PhD; Pasha, Santosh PhD*

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Abstract

Abstract: Experiments were performed to elucidate the mechanism of action of a 7-day oral administration of the sulfur-containing angiotensin-converting enzyme (ACE) inhibitor 3-thienylalanine-ornithyl-proline (TOP; 10 mg/kg/d) on endothelial dysfunction and oxidative stress compared with that of captopril (control; 40 mg/kg/d) in spontaneously hypertensive rats. The differential expression of messenger RNA by real-time reverse-transcriptase–polymerase chain reaction and protein by Western blot analysis was assessed for the markers nicotinamide adenine dinucleotide phosphate oxidase, p22phox, endothelial nitric oxide (NO) synthase, and AT1 receptor. Furthermore, TOP-induced vascular relaxation was also investigated using rat aortic rings in an organ bath. TOP significantly downregulated both messenger RNA and protein expressions of p22phox and AT1 receptor; the latter facilitates vasoconstriction through angiotensin II. In addition, TOP upregulated endothelial NO synthase, thus enhancing the production of NO. Vascular studies revealed that TOP caused endothelium-dependent vasorelaxation. In conclusion, unlike the free sulfur in captopril, the thiophene ring in TOP may act as a better scavenger of free radicals. Therefore, TOP exerted more significant antihypertensive effects than captopril, not only through angiotensin-converting enzyme inhibition but also through more effective antioxidation, because the inherent thiophene moiety resulted in the enhanced production of NO.

© 2013 Lippincott Williams & Wilkins, Inc.

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