Cholinergic neurogenic vasodilatation is mediated by nitric oxide in the dog hindlimb Academic Article uri icon


  • OBJECTIVE:The aim was to investigate the role of nitric oxide (NO) in cholinergic neurogenic vasodilatation in the dog hindlimb using the NO synthase inhibitor, N-nitro-L-arginine (NOLA), and the NO precursor, L-arginine. METHODS:20 dogs were anaesthetised with thiopentone and alpha chloralose and experiments were performed in the presence of noradrenergic neurone blockade with guanethidine (15 subcutaneously). Using stereotaxic procedures, specific sites in the hypothalamus were electrically stimulated (HS) to produce depressor and hindlimb vasodilator responses. In each experiment, responses to intra-arterial (ia) injections of acetylcholine and glyceryl trinitrate produced increases in femoral blood flow similar to those caused by HS. RESULTS:Vasodilator responses to HS and acetylcholine but not glyceryl trinitrate were reduced by the muscarinic receptor antagonists tropicamide (3-12 mg ia) or atropine (0.5 intravenously, i.v.). Administration of NOLA (5-15 ia) significantly attenuated the HS induced decrease in arterial pressure [delta AP: control = -21 (SEM 3) mm Hg v NOLA treated = -9(3) mm Hg, p < 0.005] and the increase in femoral blood flow [delta FBF: control = 43(7) ml.min-1 v NOLA treated = 17(4) ml.min-1, p < 0.005]. NOLA also significantly inhibited femoral vasodilator responses to acetylcholine [delta FBF: control = 47(6) ml.min-1 v NOLA treated = 35(6) ml.min-1, p < 0.05] whereas responses to glyceryl trinitrate were enhanced [delta FBF: control = 54(9) ml.min-1 v NOLA treated = 69(9) ml.min-1, p < 0.005]. In addition L-arginine (150-300 i.v.), but not D-arginine (150 i.v.), reversed the inhibitory effect of NOLA on HS induced dilator responses [delta FBF: NOLA treated = 14(4) ml.min-1 v L-arginine treated = 35(8) ml.min-1, n = 8; greater than NOLA treated, p < 0.05]. CONCLUSIONS:Vasodilatation in the dog hindlimb evoked by activation of cholinergic nerves involves the synthesis of NO; however the source of this NO remains to be determined.


publication date

  • April 1, 1994