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 (NOS) 1 immunoreactivity in perivascular nitrergic nerves in the iliac and sciatic arteries. Furthermore, NOS3 immunoreactivity was observed in the vascular smooth muscle of the sciatic artery, but not the endothelium. Acetylcholine (ACh) was used to facilitate intracellular Ca2+ signaling to activate vasodilatory pathways in the arteries. In the iliac artery, ACh-mediated vasodilation was abolished by blockade of the soluble guanylate cyclase pathway with the soluble guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, 10-5 M) and blockade of the prostaglandin signaling pathway with indomethacin (10-5 M). Furthermore, disruption of the endothelium had no effect on the ACh-mediated vasodilation in the iliac artery, and generic inhibition of NOS with Nω-nitro-l-arginine (3 × 10-4 M) significantly inhibited the vasodilation, indicating NO signaling. 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 Nω-nitro-l-arginine, but it was significantly inhibited by the specific NOS1 inhibitor N5-(1-imino-3-butenyl)-l-ornithine (vinyl-l-NIO, 10-4 M). ODQ mostly inhibited the ACh-mediated vasodilation. In addition, indomethacin also significantly inhibited the ACh-mediated vasodilation, indicating a role for prostaglandins 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.