Relaxation of goat detrusor muscle by L-arginine involves NO-dependent but guanylyl cyclase independent activation of K_CA channels

Urinary incontinence is a major problem both in man and animals particularly dogs. L-arginine, the precursor of NO, relaxes coronary artery smooth muscle by opening of K_ATP channels. L-arginine has beneficial circulatory effects in patients with essential and secondary hypertension. However, not much is known about the role of L-arginine on bladder physiology. In view of this, the present work investigated the functional role of L-arginine on detrusor smooth muscle of goat.

Detrusor strips of goat, collected from local abattoir were mounted in a thermostatically controlled (37°±0.5°C) organ bath (20 ml capacity) containing physiological solution. After 1 hr of equilibrium, carbachol (CCh) (10⁻⁵ M) was used to induce sub-maximal contraction. L-arginine (10⁻³ M) was added at the plateau of contraction to see any observable effect in absence and presence of modulators of NO and ion channels.

L-arginine (10⁻³ M) reversed the contractions induced by CCh (10⁻⁵ M) on detrusor tissues. Methylene blue (MB) (10⁻⁵ M), the non-specific guanylyl cyclase inhibitor, failed to attenuate the relaxant response of L-arginine but, the NO synthase inhibitor L-NAME (3x10⁻⁶ M) inhibited the relaxant response of L-arginine. The K_ATP channel blocker glibenclamide (10⁻⁶ M) failed to inhibit the relaxation induced by L-arginine while K_Ca channel blocker tetraethylammonium (TEA) (10⁻³ M) inhibited the relaxant response of L-arginine. The results of the present study suggest that L-arginine produces relaxation of goat detrusor muscle and the L-arginine-elicited relaxation is NO-dependent but guanylyl cyclase independent which activates K_Ca channels.