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 (10−9–10−5M) induced a concentration-dependent relaxation, whereas in absence of endothelium, cicletanine (10−9–10−5M) was ineffective although it relaxed the smooth muscle at higher concentrations (10−4M). At pharmacologic concentrations (below or equal 10−5M), relaxation induced by cicletanine, in presence of endothelium, was prevented by Nω-nitro- -arginine (L-NNA) (P<.005) and relaxation induced by the highest concentration (10−4M) was reversed by BaCl2 (P<.005). Under hypoxic conditions, in presence of NE and endothelium, the aorta displayed an increased developed tension that was significantly (P<.05) attenuated by cicletanine (10−5M) and insensitive to indomethacine (10−7M). When the two compounds were added together, the relaxation induced by cicletanine was significantly improved (P<.005). These results indicated that cicletanine, under stress conditions, relaxes vascular smooth muscle through an endothelium-dependent action mediated by the nitric oxide (NO) synthase pathway. We proposed that the observed vascular effects could be associated with the counter-regulation mechanisms linked to the antihypertensive action of cicletanine.