Pravastatin Preserves Vasomotor Response in Atherosclerotic Arteries after Balloon Angioplasty

Abstract: Vasodilation response to pharmacological challenge is inhibited following balloon angioplasty. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been demonstrated to enhance endothelial cell production of nitric oxide and reduce low-density lipoprotein cholesterol. This study was conducted to evaluate the effect of pravastatin on vasodilation following balloon angioplasty in normal and atherosclerotic arteries. Three normal and 3 atherosclerotic New Zealand White rabbits were used. Atherosclerosis was induced by feeding a high cholesterol diet. Rabbits were sacrificed and carotid arteries were isolated and placed in a dual perfusion chamber. Both arteries from each rabbit were perfused with oxygenated physiologic buffered solution at 37 o C and 60 mmHg. One artery was exposed to pravastatin (100 μM) and the other served as control. Balloon angioplasty (BA) was performed in both arteries using a 2.5×15 mm balloon catheter inflated to 10 atm at 3 different sites for one minute each. Pharmacological challenge was given using acetylcholine (2×10 -5 M) and sodium nitroprusside (2×10 -5 M) in norepinephrine (2×10 -6 M) preconstricted arteries. Vessel diameter was measured by a computer planimetry system. After BA in normal rabbit arteries, acetylcholine did not demonstrate significant difference in percent lumen dilation between control and pravastatin (25.5±10.4 vs 16.6±7.5, p=ns) while atherosclerotic arteries had significantly preserved vasomotor response with pravastatin (16.9±7.2 vs 33.6±18.2, p<0.005). Similar results were noted with nitroprusside in normal arteries (29.0±14.5 vs 18.0±10.5, p=ns) and atherosclerotic arteries (18.6±7.4 vs 38.4±19.8, p<0.003). Pravastatin preserved vasomotor response in atherosclerotic arteries following BA when compared to normal arteries. This effect may be due to an enhanced production of nitric oxide in atherosclerotic arteries. However, pravastatin also appears to influence vasomotor response by either non-endothelial dependent or a combination of endothelial and non-endothelial dependent mechanism