NERVE-MEDIATED RELAXATION OF THE HUMAN INTERNAL ANAL-SPHINCTER - THE ROLE OF NITRIC-OXIDE

The aim of this study was to determine if nitric oxide (NO) is the non -adrenergic, non-cholinergic neurotransmitter, released by enteric inh ibitory nerves, which mediates relaxation of the human internal anal s phincter. Isolated muscle strips were mounted for isometric tension re cording in superfusion organ baths. Sodium nitroprusside, an exogenous donor of NO, relaxed the strips in a concentration dependent manner. In the presence of atropine and guanethidine, transmural field stimula tion produced tetrodotoxin sensitive relaxations, which were inhibited in a dose dependent and enantiomer specific manner by antagonists of NO synthase; completely by L-nitroarginine and partially by L-N-monome thyl arginine. The effect of these antagonists was reversed by L-argin ine but not D-arginine. Oxyhaemoglobin, a scavenger of nitric oxide, a lso abolished the relaxations but methaemoglobin had no such effect. T hese results strongly suggest that NO is, or is very closely associate d with, the non-adrenergic, non-cholinergic neurotransmitter mediating neurogenic relaxation of the human internal anal sphincter.