Effects of SK-1080 on intimal thickening and impaired vascular relaxation after balloon injury in rats.

Abstract

We investigated the effects of SK-1080, a novel angiotensin AT(1) receptor antagonist, on neointimal proliferation in the rat carotid artery after balloon injury, together with its effects on the impaired endothelium-dependent vascular relaxation. SK-1080 (0.3 and 1.0 mg/kg/day) was orally administered in balloon-injured rats for 21 days (from 6 days before to 14 days after balloon injury). SK-1080 (1 mg/kg) exerted significant effects on three important parameters associated with the intimal thickening induced by balloon injury (50.0% reduction in neointimal area, 42.7% reduction in stenosis ratio and 69.1% increase in lumen/total area ratio). Acetylcholine-induced relaxation was significantly reduced in the balloon-injured carotid arteries (64.0 +/- 9.1%), and this impairment of acetylcholine-induced relaxation was significantly restored by SK-1080 (maximal relaxation: 87.1 +/- 6.5 and 88.6 +/- 1.9% at 0.3 and 1.0 mg/kg, respectively, p < 0.05). However, the endothelial-independent, sodium nitroprusside-induced relaxation was clearly demonstrated and did not differ in carotid arteries from all treatment groups. Furthermore, acetylcholine-induced relaxation was completely inhibited by L-NAME but not by indomethacin. SK-1080 caused a slight hypotension 1 day before balloon injury (8.7%), which gradually returned to the baseline 6 and 13 days after balloon injury. These results suggest that SK-1080 may have therapeutic potential for the treatment of vascular diseases such as restenosis and atherosclerosis.

• Authors: Byung Ho Lee, Sung-Eun Yoo, Hwa Sup Shin
• Journal: Pharmacology (Pharmacology) Vol. 66 Issue 2 Pg. 81-8 (Oct 2002) ISSN: 0031-7012 [Print] Switzerland
• PMID: 12207115 (Publication Type: Journal Article)
• Copyright: Copyright 2002 S. Karger AG, Basel

Chemical References

• KR 31080
• Pyridines
• Tetrazoles

Topics

• Animals
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Carotid Artery Injuries (drug therapy, physiopathology)
• Carotid Artery, Common (drug effects, physiopathology)
• Catheterization (adverse effects)
• Male
• Pyridines (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Tetrazoles (pharmacology, therapeutic use)
• Vasodilation (drug effects, physiology)