Figure 1.

Pharmacomechanical mechanisms influencing cavernous smooth muscle tone. The cavernous nerves provide parasympathetic input to penile smooth muscle. Branches of the hypogastric nerve and sympathetic chain convey sympathetic input to the penis. The cavernous nerves release nitric oxide (NO) and possibly vasoactive intestinal peptide (VIP) and acetylcholine (ACh). NO is synthesized from neuronal nitric oxide synthase (nNOS). NO acts through soluble guanylate cyclase to raise cGMP, thereby causing a fall in cytosolic Ca⁺², which is responsible for smooth muscle relaxation. ACh acts on vascular endothelium to release NO via endothelial nitric oxide synthase (eNOS). In addition, the endothelium produces endothelin-A (ET-A) receptors to contract cavernous smooth muscle. VIP activates adenylate cyclase, causing a rise in cAMP, with a subsequent fall in cytosolic Ca⁺². The breakdown of cAMP and cGMP is achieved primarily though phosphodiesterase (PDE) types 4 and 5A. Vasoconstrictive tone is provided by norepinephrine (NE) released from noradrenergic sympathetic nerves. NE acts in α₁-adrenergic receptors (α_1A, α_1B) to raise inositol triphosphate (IP₃). This elevates cytosolic Ca⁺² and increases smooth muscle tone.