Influence of acetylcholine, peptides, and other vasodilators on endogenous noradrenaline overflow and vasoconstriction in canine blood perfused gracilis muscle.

The effects of acetylcholine, substance P and vasoactive intestinal polypeptide (VIP) on the endogenous noradrenaline (NA) overflow were compared to those of two other vasodilators, nitroglycerin and felodipine, neither of which are thought to influence NA neurotransmission in blood perfused skeletal muscle. The lack of prejunctional effects of nitroglycerin was verified in vitro. The sympathetic nerve stimulation (SNS) evoked NA overflow was reduced by 37 +/- 9% by a dose of acetylcholine which reduced the perfusion pressure at rest by 44 +/- 6%. Conversely, atropine tended to enhance SNS evoked NA overflow. Acetylcholine reduced the vasoconstrictor responses to SNS when compared to the responses observed with an equipotent vasodilatory dose of, e.g. nitroglycerin. The SNS evoked NA overflow was not influenced by a moderate mechanical blood flow reduction or by pronounced reductions of vascular resistance induced by either substance P, VIP, nitroglycerin or felodipine, supporting the idea that the transport of NA from nerve terminal to blood is not importantly influenced by moderate decreases in blood flow or vascular tone. Prejunctional muscarinic inhibition of NA release in skeletal muscle was verified under in vivo conditions, but the other substances tested did not influence sympathetic neurotransmission. Endogenous NA overflow appears to mirror NA release in vivo also when diffusion is influenced by changes in blood flow or vascular tone in this experimental model.