Relaxation of vascular smooth muscle by cicletanine in aged wistar aorta under stress conditions - Importance of nitric oxide

The vascular mechanism of action of cicletanine, an antihypertensive agent, was studied on isolated Wistar rat aortas (24-months-old) in presence and in absence of endothelium in two different stress conditions, normoxic and hypoxic, in presence of norepinephrine (NE). Under normoxic conditions, in presence of endothelium, cicletanine (10(-9)-10(-5)M) induced a concentrati on-dependent relaxation, whereas in absence of endothelium, cicletanine (10 (-9)-10(-5)M) was ineffective although it relaxed the smooth muscle at high er concentrations (10(-4)M). At pharmacologic concentrations (below or equa l 10(-5)M), relaxation induced by cicletanine, in presence of endothelium, was prevented by NO-nitro-L-arginine (L-NNA) (P < .005) and relaxation indu ced by the highest concentration (10(-4)M) was reversed by BaCl2 (P < .005) . Under hypoxic conditions, in presence of NE and endothelium, the aorta di splayed an increased developed tension that was significantly (P < .05) att enuated by cicletanine (10(-5)M) and insensitive to indomethacine (10(-7)M) . When the two compounds were added together, the relaxation induced by cic letanine was significantly improved (P <. 005). These results indicated tha t cicletanine, under stress conditions, relaxes vascular smooth muscle thro ugh an endothelium-dependent action mediated by the nitric oxide (NO) synth ase pathway. We proposed that the observed vascular effects could be associ ated with the counter-regulation mechanisms linked to the antihypertensive action of cicletanine. (C) 2000 American Journal of Hypertension, Ltd.