Amitriptyline eliminates calculi through urinary tract smooth muscle relaxation

• Published in: Kidney international Vol. 64; no. 4; pp. 1356 - 1364
• Main Authors: Achar, Eduardo, Achar, Rosi A.N., Paiva, Therezinha B., Campos, Alexandre H., Schor, Nestor
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2003; Nature Publishing; Elsevier Limited
• Subjects: Acute Kidney Injury - drug therapy; amitriptyline; Amitriptyline - therapeutic use; Animals; Biological and medical sciences; Cats; Humans; In Vitro Techniques; Male; Medical sciences; Muscle Relaxation; Muscle, Smooth - drug effects; Muscle, Smooth - physiopathology; Nephrology. Urinary tract diseases; obstructive acute renal failure; Potassium Channels, Voltage-Gated - metabolism; Rats; Rats, Wistar; relaxation; Swine; Ureter - drug effects; Ureter - physiopathology; Urethra - drug effects; Urethra - physiopathology; Urinary Bladder - drug effects; Urinary Bladder - physiopathology; Urinary Calculi - drug therapy; Urinary lithiasis; Urinary Tract - drug effects; Urinary Tract - physiopathology; urinary tract smooth muscle; urolithiasis; voltage-dependent potassium channel; voltage-dependent potassium channel; urolithiasis; amitriptyline; urinary tract smooth muscle; obstructive acute renal failure; relaxation; Fissipedia; Animal model; Carnivora; Amitriptyline; Urinary system disease; Psychotropic; Smooth muscle; Ionic channel; Urinary tract disease; Urinary tract; Tricyclic compound; Urinary stone; Relaxation; Vertebrata; Mammalia; Animal; Cat; Lithiasis; Antidepressant agent; Potassium
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1046/j.1523-1755.2003.00222.x

Amitriptyline eliminates calculi through urinary tract smooth muscle relaxation. We investigated the effects of amitriptyline in the urinary tract smooth muscle and urolithiasis. Cats presenting with obstructive acute renal failure (ARF) received amitriptyline, and renal function and survival rates were analyzed. Isometric contractions and membrane potentials of rat, pig, or human isolated urinary tract smooth muscle were recorded in the presence or absence of amitriptyline. Twenty cats with obstructive ARF caused by urethral plugs received amitriptyline. In all cases, plugs were completely eliminated, and renal function returned to normal, with a 100% survival rate in the follow-up. Amitriptyline produced potent relaxations in rat urethral strips, accompanied by significant reductions in urethral ring membrane potential. This effect was prevented by pretreatment of urethral rings with 4-aminopyridine (4-AP), a voltage-dependent potassium channel blocker. Amitriptyline abolished in a reversible manner acetylcholine-, bradykinin-, and KCl-induced contractions in rat isolated bladder, and this effect was also prevented by 4-AP. Of interest, spontaneous and KCl-induced contractions of pig and human isolated ureter were also blocked by amitriptyline. Our results indicate that amitriptyline is an effective and potent relaxant of urinary tract smooth muscle and this effect is mediated by opening of voltage dependent–potassium channels. We suggest that amitriptyline administration may help to promote elimination of urinary calculi.