Effects of SK-1080 on intimal thickening and impaired vascular relaxation after balloon injury in rats.
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.
Screening and Toxicology Research Center, Korea Research Institute of Chemical Technology, Taejon, South Korea. bhlee@krict.re.kr
Byung Ho
BH
Lee
Sung-Eun
SE
Yoo
Hwa Sup
HS
Shin
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000503:physiopathology*; D002404:Catheterization / Q000009:adverse effects*; D008297:Male; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
C111727:KR 31080; D011725:Pyridines; D013777:Tetrazoles