Nitrergic relaxation of the horse corpus cavernosum. Role of cGMP.

The research study investigates the role of nitric oxide (NO) in inducing relaxation in horse penile tissue (corpus cavernosum) through neurogenic mechanisms. The findings suggest that NO, present in nerve fibres in the corpus cavernosum, relaxes smooth muscle through a mechanism dependent on guanylate cyclase.

Nitric Oxide and Neurogenic Relaxation

• The team performed the study on the corpus cavernosum of horses to understand the role of NO in neurogenic relaxation which is the process by which nerve stimulation leads to muscle relaxation.
• A specific enzyme responsible for NO production, NADPH-diaphorase activity, was observed in nerve fibres around the arteries and muscular bundles in the trabecular tissue of the horse.
• Inducing relaxation in the corpus cavernosum via electrical field stimulation revealed that these neurogenic relaxations are sensitive to tetrodotoxin, suggesting these relaxations are being mediated by the action of nerve cells.

Investigating the Mechanism behind Neurogenic Relaxation

• When the researchers used the NO synthase inhibitor, L-NO-Arginine, it prevented the relaxations induced by electrical stimulation. This effect was reversed by the addition of L-arginine, suggesting the key role of NO in these relaxations.
• Researchers used an exogenous source of NO, which led to relaxations that were not affected by the inhibition of NO synthase. This further supported the idea that NO plays a central part in muscle relaxation mechanism.
• A substance called ODQ, used to inhibit the activation of guanylate cyclase by NO, reduced relaxations induced by electrical stimulation and exogenous NO. Thus suggesting the relaxation is not just dependent on NO but also on the activation of guanylate cyclase.

Evaluating the Involvement of Calcium and ATP-sensitive Potassium Channels

• The research team used two substances to inhibit large and small conductance calcium-activated potassium channels; however, these inhibitors did not affect the relaxations induced by NO. This suggests that these potassium channels, which are often associated with muscle activity, do not play a significant role in these relaxations.
• Similarly, the use of glibenclamide, a blocker of ATP-sensitive potassium channels, did not modify the relaxations induced by NO, suggesting that ATP-sensitive potassium channels are also not involved.

In conclusion, the study strongly indicates that NO relaxes smooth muscle in the horse corpus cavernosum primarily through a mechanism dependent on guanylate cyclase, while calcium-activated and ATP-sensitive potassium channels do not appear to have a substantial role.