Modulation of arterial reactivity using amlodipine and atorvastatin measured by ultrasound examination (MARGAUX).

OBJECTIVE: To evaluate the effect of the calcium channel blocker amlodipine on endothelial function in normotensive patients with coronary disease taking concomitant atorvastatin therapy. METHODS AND RESULTS: Atorvastatin was titrated (10-80 mg/day) to maintain LDL-C<2.5 mmol/L and patients were randomized to receive amlodipine (5-10mg/day, n=64) or placebo (n=70) for 12 months. Brachial artery flow-mediated vasodilation (FMD) was assessed using vascular ultrasound. Inflammatory markers were also measured. At 12 months there was a significant decrease in mean low-density lipoprotein cholesterol (LDL-C) (4.4-2.1 mmol/L, P<0.0001), high-sensitivity C-reactive protein (hsCRP) (3.8-2.3mg/L, P<0.0001) and soluble vascular cell adhesion molecule-1 (sVCAM-1) (710-665 ng/mL, P<0.0001) for all patients, compared with baseline. Amlodipine was associated with a mean blood pressure reduction of 8/3 mm Hg (P<0.0001) whereas patients on placebo had no significant change. In the atorvastatin-placebo group, mean FMD increased (7.3-9.5%, P<0.05) with no change in nitroglycerin-mediated dilation. No further benefit on FMD or inflammatory markers was observed with the addition of amlodipine. CONCLUSIONS: Intensive reduction of LDL-C with atorvastatin improves endothelium-dependent vasodilation and reduces markers of inflammation in patients with coronary disease. Amlodipine was not associated with a significant additional benefit on these variables.

Urotensin II and cardiovascular diseases.

Urotensin II (UII) has been found to be a potent vasoactive peptide in humans and in a number of relevant animal models of cardiovascular disease such as the mouse, rat and other non-human primates. This peptide with structural homology to somatostatin was first isolated from the urophysis of fish and was recently found to bind to an orphan receptor in mouse and human. Initially found to have potent vasoconstrictive activities in a variety of vessels from diverse species, it has also been shown to exert vasodilatation in certain vessels in the rat and human by various endothelium-dependent mechanisms. The various vasoactive properties of UII suggest that the peptide may have a physiological role in maintaining vascular tone and therefore may have a role in the pathophysiology of a number of human diseases such as heart failure. Moreover, UII has also been implicated as a mitogen of vascular smooth muscle cells suggesting a deleterious role in atherosclerosis and coronary artery disease. In addition, there is evidence to demonstrate that UII has multiple metabolic effects on cholesterol metabolism, glycemic control and hypertension and therefore may be implicated in the development of insulin resistance and the metabolic syndrome.