Endothelial preserving actions of a nitric oxide donor in carotid arterial intimal injury.
We examined the actions of a nitric oxide donor, CAS754, in a rat model of carotid artery intimal injury. Seven days following injury, the injured carotid arteries were studied for endothelial release of nitric oxide (NO) and for histological measurement of the intimal/medial (I/M) ratio. Basal release of NO was assessed by NG-nitro-L-arginine methyl ester (L-NAME)-induced vasocontraction. L-NAME contracted injured rat carotid artery rings about 27% of that obtained in control rats (p < 0.01). However, CAS754 given at 30 mcg/day i.v. resulted in a L-NAME contraction of twice that of vehicle-treated rats (p < 0.01). A control compound lacking the NO moiety (C-3934) yielded a contraction to L-NAME comparable to untreated injured rats. We also tested the ability of rat carotid artery rings to relax to the endothelium-dependent vasodilators, acetylcholine and A23187. ACh (10 mcM) relaxed carotid artery rings only about 20% of control values in vehicle-treated and in C-3934-treated rats, compared with a vasorelaxation of over 80% of control in CAS754-treated rats (p < 0.01). Relaxation to acidified NaNO2 (100 mcM) was not significantly different among any of the groups of carotid arteries, indicating normal vascular smooth muscle responses following intimal injury. Morphometric assessment of carotid arteries isolated from injured rats given either vehicle or C-3934 showed marked intimal thickening with an average intimal/medial (I/M) ratio of 0.79 +/- 0.05 and 0.73 +/- 0.06, respectively, compared with 0.10 +/- 0.02 in non-injured arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Guo
J P
JP
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
Siegfried
M R
MR
Lefer
A M
AM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013558:Sydnones / Q000378:metabolism* / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D014665:Vasodilator Agents / Q000378:metabolism* / Q000494:pharmacology*
D013558:Sydnones; D014665:Vasodilator Agents; C072857:3-(cis-2,6-dimethylpiperidino)sydnonimine; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester