BERKELEY, CA (UroToday.com) - The corpus cavernosum exhibits biochemical and physiological properties similar to the vasculature; hence, considered by many to be a specialised blood vessel.
Angiotensin II (Ang II), a bioactive octapeptide and a known modulator of regional blood flow, has long been viewed as a key mediator of corpus cavernosal smooth-muscle (CCSM) contraction/tone, playing a prominent role in the termination of penile erection. In the present study, we have identified Ang II-containing cells in the endothelium of arterioles, as well as the endothelium-lining sinusoids and smooth-muscle bundles of the human corpus cavernosum by immunohistochemistry. These cells secrete their Ang II content on adrenergic stimulation, resulting in AT1 receptor activation with the physiological development of oxidative stress (OS). This sequence of events keeps the smooth muscle of the penile arteries and trabeculae contracted, a scenario that has added significance since the CCSM cells spend the majority of the time contracted during penile flaccidity/detumescence. This is supported by the finding that human corpus cavernosum produces and secretes physiological amounts of Ang II—as much as 200-fold greater than that found in the plasma during this phase.
Our study also uses pharmacological profiling to provide direct evidence of the role of Ang II on human CCSM contractility, as well as its influence on OS and interaction with nitric oxide (NO). Ang II decreases NO bioavailability by promoting superoxide formation, which interacts with NO-inducing, smooth-muscle contraction. Consequently, inhibitors of superoxide production significantly reduce the Ang II-induced contraction, as did losartan (AT1 receptor antagonist). The deleterious effect Ang II has on penile erection has been demonstrated using anesthetised dogs, where intracavernosal injections of the octapeptide terminated spontaneous erections. In contrast, losartan induced penile erections by relaxing CCSM affecting tone and contractility of vascular smooth muscle within the blood vessels embedded in the corporal bodies, as well as the corpus cavernosum itself.
The notion that CCSM cells increase their contractile properties under pathological conditions has been reported previously, prompting the suggestion that augmented corporal, vascular, smooth-muscle contractility may contribute to the pathophysiology of erectile dysfunction (ED) in older men. This observation adds greater clinical importance to the losartan-induced inhibition of Ang II. Although cGMP-specific phosphodiesterase type 5 inhibitors (PDE 5 inhibitors) have become effective oral agents for the treatment of ED, it has become increasingly apparent that not all patients respond to this form of therapy; moreover, some who initially respond develop tachyphylaxis or discontinue their use due to loss of efficacy. Thus, the use of an Ang II antagonist, which reduces CCSM contractility, in conjunction with a PDE 5 inhibitor that increases CCSM relaxation, may be of benefit; not only by reducing the percentage of zero responders but also the concentration of PDE 5 inhibitor required to maintain erection.
Written by:
Cecil S. Thompson, PhD., as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
