Different vasodilator mechanisms in intermediate- and small-sized arteries from the hindlimb vasculature of the toad, Rhinella marina

In this study, myography was used to determine the effect of arterial size on nitric oxide (NO) vasodilatory mechanisms in the hindlimb vasculature of the toad, Rhinella marina. Immunohistochemical analysis showed NO synthase 1-immunoreactivity (NOS1-IR) in perivascular nitrergic nerves in the iliac and sciatic arteries. Furthermore, NOS3-IR was observed in the vascular smooth muscle of the sciatic artery but not in the endothelium. Acetylcholine (ACh) was used to facilitate intracellular calcium signalling in order to activate vasodilatory pathways in the arteries. In the iliac artery, ACh-mediated vasodilation was abolished by blockade of both the soluble guanylate cyclase (sGC) and prostaglandin (PG) signalling pathways with the sGC inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 10-5 M), and indomethacin (10-5 M), respectively. Furthermore, disruption of the endothelium had no effect on the ACh-mediated vasodilation in the iliac artery, and generic inhibition of NOS with L-NNA ( Nω-nitro-L-arginine, 3 x 10-4 M) significantly inhibited the vasodilation, indicating NO signalling. In contrast to the iliac artery, ACh-mediated vasodilation of the sciatic artery had a significant endothelium-dependent component. Interestingly, the vasodilation was not significantly affected by L-NNA but the specific NOS1 inhibitor, vinyl-L-NIO (10-4 M) did significantly inhibit it. ODQ mostly inhibited the ACh-mediated vasodilation. In addition, indomethacin also significantly inhibited the ACh-mediated vasodilation indicating a role for PGs in the sciatic artery. This study found that the mechanisms of vasodilation in the hindlimb vasculature of R. marina vary with vessel size, and that the endothelium is involved in vasodilation in the smaller sciatic artery.