Effects of cloricromene on the levels of endothelin and on the microcirculatory function in peripheral atherosclerotic arteriopathies.
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.