Sulfur-containing angiotensin-converting enzyme inhibitor 3-thienylalanine-ornithyl-proline activates endothelial function and expression of genes involved in Renin-Angiotensin system.

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.

Rationally designed chimeric peptide of met-enkephalin and FMRFa-[D-Ala2,p-Cl-Phe4]YFa induce multiple opioid receptors mediated antinociception and up-regulate their expression.

The physiological role of NPFF/FMRFa family of peptides appears to be complex and exact mechanism of action of these peptides is not yet completely understood. In same line of scrutiny, another analog of YGGFMKKKFMRFamide (YFa), a chimeric peptide of met-enkephalin and FMRFamide, was rationally designed and synthesized which contain D-alanine and p-Cl-phenylalanine residues at 2nd and 4th positions, respectively i.e.

Endogenous peptide: Met-enkephalin-Arg-Phe, differently regulate expression of opioid receptors on chronic treatment.

Endogenous peptide, Met-enkephalin-Arg-Phe (Tyr-Gly-Gly-Phe-Met-Arg-Phe; MERF) induces effects like antinociception, inhibit contraction of guinea pig ileum, mouse vas deferens and anti-tussive action. However, results regarding its functional efficiency and selectivity are controversial. Therefore, present study was undertaken to investigate whether MERF on systemic (intra-peritoneal, i.

Effect of varying chain length between P(1) and P(1') position of tripeptidomimics on activity of angiotensin-converting enzyme inhibitors.

One of the efficient modes of treatments of chronic hypertension and cardiovascular disorders has been to restrain the formation of angiotensin-II by inhibiting the action of angiotensin-converting enzyme (ACE) on angiotensin-I. The efforts continue towards achieving superior molecules or drugs with improved affinities, better bioavailability and thus to achieve long duration of action with minimum side effects. Previously, we reported a library of tripeptidomimics of Ornithyl-Proline (Orn-Pro) conjugated with various unnatural amino acids and carboxylic acid derived heterocyclics based on the SAR studies of existing ACE inhibitors.