Continuing the theory of priapism and altered blood flow in the penis, Frank Hinman Jr hypothesized that the etiology of idiopathic priapism was vascular stasis and reduced venous outflow. Hinman found dark, viscous deoxygenated blood after aspiration in patients with priapism. This theory was supported by similar findings in patients with sickle-cell disease viagra in australia, hemodialysis patients, trauma, or malignant infiltration of the corpora cavernosa. He theorized that the ischemia created a vicious cycle of combined deoxygenated blood (hypoxic and hypercarbic) associated with venous congestion, which increased the deformity of red cells.

Burt noted bright red blood after incision and irrigation of the corpora in a patient with priapism after traumatic coitus. This increased arterial inflow in priapism was later classified by Hauri as high flow priapism. This non-ischemic priapism was recognized to be the result of a fistula between the cavernous artery and lacunar space. This allowed blood to bypass the high resistance in the helicine arteries.

Molecular Pathology

However, the rheologic changes previously theorized could not completely explain all types of priapism that were seen. This led to extensive research, which recognized that ischemic priapism was due to an imbalance of vasoconstrictive and vasodilatory forces in the corpora cavernosa. Vasoconstrictive factors included the RhoA/Rho kinase pathway, and the vasodilatory forces include the nitric oxide (NO) pathway.

A normal erection requires an intact central nervous system, peripheral nervous system, penile arterial supply, and trabecular smooth muscle. Erection involves a delicate interplay of neuronal stimulation, smooth muscle relaxation, increased arterial inflow, and reduced venous outflow. NO plays an important role in the regulation of normal erections with Canadian pharmacy viagra store. NO released from the endothelium (eNO) or nerve endings (nNO) diffuses to the smooth muscle and binds to guanylate cyclase. This leads to the conversion of guanosine triphosphate (GTP) to 3,5 cyclic guanosine monophosphate (GMP). Cyclic GMP acts as a second messenger and binds with a cGMP-dependent protein kinase which exerts itself on ion channels. Ultimately, smooth muscle intracellular calcium levels are lowered and this inhibits myosin light chain kinase, thus inhibiting the cross linking of actin and myosin.

This leads to smooth muscle relaxation and vasodilatation. cGMP-dependent protein kinase also regulates smooth muscle con-traction via the RhoA/Rho-kinase pathway. The RhoA/Rho kinase pathway is a calcium independent pathway, which is the predominant mechanism controlling corporal smooth muscle contraction. RhoA is a member of the Ras low molecular weight of guanosine triphosphate-binding proteins, and mediates agonist-induced activation of Rho-kinase. Rho-kinase phosphorylates and reduces the activity of myosin phosphatase, contributing to myosin light chain kinase phosphorylaion. cGMP-dependent protein kinase also directly phosphorylates RhoA and downstream effectors of the RhoA/Rho kinase pathway. The net effect is smooth muscle contraction. The activities of cGMP are kept under balance by its degradation by the enzyme phosphodiesterase type 5 (PDE5).

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