Investigation of cavernosal smooth muscle dysfunction in low flow priapism using an in vitro model

Abstract

The effects of hypoxia (pO 2 : 50 mmHg), acidosis (pH: 6.9) or glucopenia (absence of glucose) in vitro on the tone of the rabbit corpus cavernosum were investigated. The recovery of smooth muscle contractility following exposure to these conditions was also assessed. Hypoxia, acidosis or glucopenia alone or in combination showed a sustained reduction in the tone. Reperfusion of tissue strips showed complete recovery of smooth muscle tone for all conditions except when hypoxia and glucopenia were combined or when hypoxia, glucopenia and acidosis were used in combination. Incomplete recovery of tone was associated with a significant reduction in tissue ATP concentrations and an increase in the number of TUNEL (terminal deoxynucleotidyl transferasemediated dUTP nick-end labelling)-positive nuclei. This indicates that following reversal of hypoxia, acidosis and glucopenia, failure of conventional a-adrenergic agonists to produce tumescence in low flow priapism is associated with irreversible smooth muscle cell dysfunction, which is linked to ATP reduction and smooth muscle cell death.

Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

“…The maximum phenylephrine-induced contraction was reached within 10-20 s of application to CCSs from Ada + and Ada -/-mice. Electrical field stimulation (EFS) is commonly used to stimulate the nerves that innervate the smooth muscle cells of the corpus cavernosum to mediate smooth muscle relaxation, corresponding to normal physiological penile erection (12,27,28,30,31). In our studies, EFS induced relaxation of CCSs from both Ada + and Ada -/-mice in a voltage- and frequency-dependent manner ( Figure 1, B and C).…”

“…The particular EFS parameters of 0-30 V and 30 Hz, with a pulse width of approximately 0.5 ms, are commonly used in mice. Available evidence indicates that these electrical field strength parameters stimulate only neurons, not muscle, and thus are thought to mimic normal penile erection (27,28,31). The concentrations of cAMP and cGMP in CCSs were subsequently determined (see below).…”

“…To further confirm our in vivo observation, we functionally tested the effect of PEG-ADA on EFS-induced relaxation of CCSs from Ada -/-mice. This is a commonly used and well-accepted functional assay of penile vascular responses in multiple species (12,27,28,30,31). CCSs of Ada -/-mice achieved maximal relaxation with 5 V and 30 Hz stimulation ( Figure 1, B and C).…”

Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway

“…As it was difficult to use rat CC strips in organ bath for mechanism studies, rabbit's CC strips were commonly used as described previously. 15,[20][21][22] It has been reported that nonginkgolide nonflavonoid fraction of ginkgo biloba extract (NGE) has the most potent relaxing effect on vascular smooth muscle. In the tissue precontracted by norepinephrine (10 À5 M), corpus cavernosal tissue of human and rabbit showed relaxation in response to subfractions of NGF in a dose-dependent manner.…”

Recent Advances in the Medical and Surgical Treatment of Priapism

“…Studies based on animal models have shown impaired response of cavernosal smooth muscle to sympathomimetic agents in the acidotic, hypoxic, and glucopenic conditions that develop during prolonged ischemia [6]. While at least one study reports safe resolution of ischemic priapism using high-dose phenylephrine (1,000 μg repeated every 5 min) [7], another suggests no benefit over conventional doses in cases of prolonged ischemia [8].…”