PubMed · 11399241
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R D Higgins, M Keszler. 2001. Perinatal vascular development.. https://doi.org/10.1016/s0008-6363(01)00334-0
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The effects of an infusion of the neurosteroid pregnenolone sulfate into the medial septum on acetylcholine release in the hippocampus and on spatial memory were evaluated in two experiments. Results show that pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline and improved recognition memory of a familiar environment. Therefore, our results suggest that the septo-hippocampal pathway could be involved in the promnesic properties of this neurosteroid.
After menopause, most healthy women show an impairment of peripheral vasodilation and an increase of plasma cholesterol levels. Statins have been shown to improve endothelial function in hypercholesterolemic men and women. The present study tests whether atorvastatin (10 mg) influences endothelium-dependent vasodilation in postmenopausal normocholesterolemic women. Twenty-eight healthy, postmenopausal women (mean age 51 +/- 2 years) with serum total cholesterol and low-density lipoprotein cholesterol within the desirable range entered a double-blind, single-crossover study. Postmenopausal women were randomized to receive either atorvastatin (10 mg/day) or placebo for 10 days and then crossed to the complementary treatment. Endothelium-dependent and -independent responses were assessed by means of strain-gauge plethysmography before and after intra-arterial infusion of acethylcholine (ACh) and sodium nitroprusside, in comparison to physiologic saline. The nitric oxide pathway was evaluated by repeating the infusion of ACh during admininstration of L-arginine and (G)-monomethyl-L-arginine (L-NMMA). Serum lipoproteins were not significantly modified by the active treatment. The vasodilation induced by ACh was significantly higher in the atorvastatin-treated women compared with the placebo-treated group (24 +/- 3 vs 13 +/- 2 ml/100 ml tissue/min, p <0.01). In contrast, responses to the endothelium-independent vasodilator sodium nitroprusside were not significantly modified by atorvastatin. The ACh-stimulated vasodilation induced by atorvastatin was additionally potentiated by L-arginine (800 +/- 105% vs 370 +/- 60%, p <0.05) and blunted by L-NMMA. No correlation was found between changes in plasma cholesterol and improvement in forearm blood flow. Our data show that the beneficial effect of atorvastatin on endothelium-dependent vasodilation is independent from changes in the lipid profile.
BACKGROUND: Manipulating gene expression in the failing heart has therapeutic promise, but until now efficient and homogeneous cardiac gene delivery has required an open-chest approach. This study examines the hypothesis that vector delivery promoted by echo contrast microbubbles will be maximized by injection of the vectors into the aortic root with brief balloon occlusion above the sinuses, while at the same time prolonging diastole and vasodilating with acetylcholine (ACh) to maximize coronary exposure. METHODS AND RESULTS: After incubation with albumin-coated perfluorocarbon microbubbles, an adenovirus encoding a reporter gene was infused into the aortic root of rats. To maximize delivery, the aortic root was transiently occluded with a balloon catheter during a brief ACh-induced asystole. Ultrasound was used to image the delivery and disrupt the microbubbles. Aortic occlusion with concomitant ACh increased myocardial gene expression for virus + microbubbles by >2.5-fold, from 925+/-165 to 2358+/-376 relative units (RU; P<0.01). This delivery system also produced substantial expression with vector alone (1473+/-549 RU). All uptakes were significant compared with 433+/-332 RU without virus. CONCLUSIONS: An adenoviral delivery system combining echo contrast with a catheter-based technique to maximize coronary perfusion increases gene delivery compared with echo contrast alone. This novel method permits efficient percutaneous gene delivery in closed-chest animals.