Urology>>>>>Andrology
Question 1#

Phosphodiesterase 5 inhibitors cause:

a. Increased (nitric oxide) NO breakdown
b. Increased NO levels in penile endothelium
c. Increased disintegration of free oxygen radicals
d. Increase cGMP levels
e. Decreases cAMP levels

Correct Answer is D

Comment:

Answer D

NO is released either at non-adrenergic non-cholinergic nerve terminals (nitrergic) on the cavernous smooth muscle cell or on the endothelial cell lining of the sinusoids. Through membrane-bound G proteins, NO activates guanylate cyclase, which induces cleavage of guanosine triphosphate to 3′,5′-cyclic guanosine monophosphate (3′,5′-cGMP). The smooth muscle-relaxing effects of NO are mediated by this second messenger (cGMP). Cyclic GMP activates protein kinase G, which phosphorylates proteins at the so-called maxi-potassium channels. This results in an outflow of potassium ions into the extracellular space with subsequent hyperpolarisation, with inhibition of voltage-dependent calcium channels and therefore a decrease in intracellular calcium ion concentrations. The intracellular decline in calcium ions suppresses the activity of myosin light chain kinase and thus increases the intracellular content of dephosphorylated myosin light chain, which enables the smooth muscle cell to relax. The enzyme phosphodiesterase type 5 inactivates cGMP and thereby reduces relaxation. By inhibiting this enzyme, PDE5 inhibitors promote smooth muscle relaxation in the corpus cavernosum by increasing the cGMP concentration.