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Cholinergic neurogenic vasodilatation is mediated by nitric oxide in the dog hindlimb
K E Loke1, C G Sobey, G J Dusting
1Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
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 mg.kg-1 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 mg.kg-1 intravenously, i.v.). Administration of NOLA (5-15 mg.kg-1 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 mg.kg-1 i.v.), but not D-arginine (150 mg.kg-1 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.