Effects of Cloricromene on the Levels of Endothelin and on the Microcirculatory Function in Peripheral Atherosclerotic Arteriopathies

Abstract

The effects of cloricromene on plasma endothelin-1 (ET-1) levels and on microcirculatory function in 9 patients with peripheral atherosclerotic arteriopathy (PAA) and in healthy control subjects were studied. ET-1 levels and microcirculatory function were evaluated both under basal conditions and 30, 60, and 90 min after acute administration of cloricromene (30 mg i.v.). PAA patients had significantly increased levels of ET-1 and impaired vascular parameters (studied by means of Winsor’s Index, Gosling’s Index, postischemic perfusion index and recovery time) when compared to control subjects. The acute administration of cloricromene (30 mg i.v.) did not change plasma ET-1 both in control subjects and in patients with PAA. In contrast, cloricromene produced a significant improvement in the postischemic perfusion index and in recovery time in arteriopathic patients. Control subjects and patients with PAA also underwent a cold pressor test (CPT) under basal conditions and (72 h later) 30 min after an acute intravenous administration of cloricromene (30 mg i.v.). CPT caused a higher increase in ET-1 in the patients with PAA compared to the control group, and a reduction in the vascular flow at the femoral level, while the pretreatment with cloricromene prevented both the increase in the levels of ET-1 and the reduction of the femoral vascular flow observed after the cold stimulus in patients with PAA. Our data show that cloricromene, besides ameliorating the microcirculatory function, is able to interfere with dynamic mechanisms, such as those induced by the CPT, capable of stimulating the release of ET-1 at the vascular level.

Cloricromene effect on the enzyme activities of the tryptophan–nicotinic acid pathway in diabetic/hyperlipidemic rabbits

“…Since cloricromene influences TNF-a production, the drug has been recently evaluated on an animal model of inflammatory bowel disease (Fries et al, 2004), where TNF-a has a key role; the drug significantly reduced the tissue concentrations of TNF-a and myeloperoxidase activity, whereas no effect was seen on blood coagulation parameters (Fries et al, 2004). In addition, cloricromene is able to influence the release of endothelin-1 in patients with peripheral atherosclerotic arteriopathies (Saitta et al, 1996) and it possesses a notable inhibitory effect on polymorphonuclear neutrophil function (Groban et al, 1998;Zatta and Bevilacqua, 1999). In our experience, cloricromene is able to regenerate rabbit aortic endothelium after cryoinduced vascular damage, as demonstrated by morphological features at scanning electron microscopy (Aliev et al, 1999).…”