Non-adrenergic, non-cholinergic vascular control with reference to neuropeptide Y, vasoactive intestinal polypeptide and nitric oxide.

1. NOS-immunoreactivity was shown to be colocalized with vasoactive peptides such as VIP, PHI and NPY in postganglionic parasympathetic neurons to the submandibular gland. NOS-immunoreactivity was on the other hand found in preganglionic neurons in sympathetic ganglia but only in few postganglionic sympathetic neurons. These latter neurons also contained VIP and PHI. NPY was present in postganglionic perivascular sympathetic nerves in all organs studied. 2. Large vasoconstrictor responses were evoked by sympathetic nerve stimulation in the pig and dog after depletion of NA by reserpine treatment combined with interruption of nerve activity. Reserpine resistant vascular responses were obtained already at single pulse stimulation in pig skeletal muscle but the sensitivity to nerve stimulation varied with type of vascular bed. In general, the maximal vasoconstriction obtained after reserpine treatment was smaller than in controls but the duration of the response was prolonged. 3. In control condition NPY overflow was relatively well maintained. The severalfold larger NPY-overflow obtained after reserpine treatment compared to control conditions contributes to the gradual peptide depletion upon repeated stimulation and is likely to be related to lack of prejunctional alpha 2-adrenoceptor inhibition of transmitter release. NPY also regulated transmitter release via a prejunctional action. The NPY-LI in splenic venous effluent upon sympathetic stimulation after reserpine reached levels where exogenous NPY causes vasoconstriction. 4. NPY and NPY analogues caused long-lasting vasoconstriction. The dominating vascular NPY receptor seemed to be of the Y1 type, which mediated vasoconstriction in all vascular beds investigated and also increased MABP. A population of postjunctional Y2 receptors was also present in the splenic vascular bed in addition to its prejunctional localization on sympathetic nerves. 5. Inhibition of NO production by L-NNA caused general vasoconstriction, reduction in cardiac output and increase in MABP. L-NNA caused larger vasoconstriction in intact than in sympathetically denervated hind limb. After inhibition of NO production, preganglionic sympathetic nerve stimulation of the hind limb and nasal mucosa had vasoconstrictor effects only slightly different from those seen in control conditions. Both the cholinergic and non-cholinergic components of the parasympathetic nerve-mediated vasodilatation in the submandibular salivary gland were on the other hand markedly suppressed by L-NNA. 6. VIP- and ACh-evoked vasodilatory effects in the submandibular salivary gland were reduced after NOS-inhibition. Also the overflow of NPY-LI evoked by parasympathetic nerve stimulation of the submandibular salivary gland was suppressed by L-NNA.(ABSTRACT TRUNCATED AT 400 WORDS)