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 o n microcirculatory function in 9 patients with peripheral atherosclero tic arteriopathy (PAA) and in healthy control subjects were studied. E T-1 levels and microcirculatory function were evaluated both under bas al conditions and 30, 60, and 90 min after acute administration of clo ricromene (30 mg i.v.). PAA patients had significantly increased level s of ET-1 and impaired vascular parameters (studied by means of Winsor 's Index, Gosling's Index, postischemic perfusion index and recovery t ime) when compared to control subjects, The acute administration of cl oricromene (30 mg i.v.) did not change plasma ET-1 both in control sub jects and in patients with PAA. In contrast, cloricromene produced a s ignificant improvement in the postischemic perfusion index and in reco very time in arteriopathic patients. Control subjects and patients wit h PAA also underwent a cold presser test (CPT) under basal conditions and (72 h later) 30 min after an acute intravenous administration of c loricromene (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 th e vascular flow at the femoral level, while the pretreatment with clor icromene prevented both the increase in the levels of ET-1 and the red uction of the femoral vascular flow observed after the cold stimulus i n patients with PAA. Our data show that cloricromene, besides ameliora ting the microcirculatory function, is able to interfere with dynamic mechanisms, such as those induced by the CPT, capable of stimulating t he release of ET-1 at the vascular level.