Comparison of the effects of nitric oxide donors and calcium channel blockers on the intrinsic myogenic tone of sheep isolated internal anal sphincter

Abstract

Chronic anal fissure is associated with considerable pain and anal hypertonia. Numerous clinical studies attest to the effectiveness of individual nitro-containing drugs and organic calcium channel blockers in this condition but there are few comparative studies. Isolated segments of sheep internal anal sphincter were prepared for isometric tension recording. The effect of various drugs on myogenic tone was examined in the absence or presence of sodium orthovanadate (SOV), an agent used to mimic anal hypertonia by increasing myogenic tone. All the drugs tested produced concentration-dependent inhibition of myogenic tone, with the maximum effect ranging from 66.4 per cent (verapamil) to 100 per cent (sodium nitroprusside). Sodium nitroprusside and diltiazem were the most potent, followed by glyceryl trinitrate (GTN), nifedipine and verapamil, which had similar potency, and finally nicorandil. The potency of GTN and diltiazem was reduced threefold in the presence of 1 mmol/l SOV. The combined effect of GTN and diltiazem was greater than the effect of either agent alone, even in the presence of 3 mmol/l SOV. Nitro-containing drugs and organic calcium channel blockers are potent inhibitors of anal sphincter myogenic tone that may be used in combination to treat chronic anal fissure.