Functional evidence that balloon angioplasty results in transient nitric oxide synthase induction.
Since serious vasospastic episodes limit the efficacy of percutaneous transluminal coronary angioplasty, this study has examined the time-dependent changes in vascular reactivity that occur following rat carotid artery balloon angioplasty. Relative to vessels from sham-operated animals, angioplasty caused an immediate increase in endothelin-1 contractile potency, an observation not made with noradrenaline or KCl, implicating endothelin-1 in the pathogenesis of acute arterial vasospasm. This hyperreactivity, possibly resulting from the loss of endothelin-1-induced nitric oxide release from the endothelium, was transient and was followed by a non-specific decrease in reactivity to all three spasmogens. Since the delayed reduction in endothelin-1 contractile potency was restored by N omega-nitro-L-arginine methyl ester, this hyporeactivity appeared to result from nitric oxide synthase induction. Furthermore, since the regenerating endothelium was dysfunctional, the generation of nitric oxide was from a non-endothelial source (possibly the smooth muscle or infiltrating macrophages). This response may function to ameliorate the spasmogenic and proliferative actions of chronically acting vasoactive factors and oppose platelet aggregation.
Douglas
S A
SA
Department of Cardiovascular Pharmacology (UW2510), SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Vickery-Clark
L M
LM
Ohlstein
E H
EH
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D017536:Carotid Artery, Common / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004790:Enzyme Induction / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
D016232:Endothelins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011189:Potassium Chloride; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine