FLOSEQUINAN DOES NOT AFFECT SYSTEMIC AND REGIONAL VASCULAR-RESPONSES TO SIMULATED ORTHOSTATIC STRESS IN HEALTHY-VOLUNTEERS

1 The effects of a single oral dose (100 mg) of flosequinan on systemic and regional (forearm, splanchnic and renal) vascular responses to simulated orthostatic stress (lower body negative pressure, LBNP) were investigated in nine healthy male volunteers, in a double-blind, placebo-controlled crossover study. 2 Forty-five minutes after its administration and before LBNP, flosequinan induced a significant decrease in total peripheral and in forearm vascular resistances without any concomitant change in arterial pressure, in heart rate and in the investigated biological parameters (plasma catecholamines, arginine vasopressin and renin activity). 3 After flosequinan and placebo, LBNP induced similar decreases in central venous pressure at all levels of LBNP (-10, -20 and -40 mm Hg) and in pulse pressure at LBNP -40 mm Hg. LBNP-induced increase in forearm vascular resistance was significantly more marked after flosequinan than after placebo at all levels of LBNP, and this was also true for splanchnic vascular resistance but at LBNP -40 mm Hg only. However, inasmuch as the basal values of these two parameters before LBNP were lower after flosequinan than after placebo, their final values after LBNP -40 mm Hg were similar. Finally, LBNP-induced changes in renal vascular resistance. glomerular filtration rate and filtration fraction as well as in plasma catecholamines. arginine vasopressin and renin activity were similar after flosequinan and placebo at all levels of LBNP. 4 Flosequinan affected neither reflex control of heart rate (phenylephrine test) nor non-specific vasoconstrictor responses (cold pressor test). 5 Thus, in healthy volunteers, the vasodilating properties of flosequinan do not interfere with the adaptative neurohumoral responses which allow the maintenance of arterial blood pressure and the preservation of renal homeostasis during simulated orthostatic stress or moderate volume depletion.