Calpain Inhibition Improves Erectile Function in a Rat Model of Cavernous Nerve Injury

Abstract

Introduction: Erectile dysfunction (ED) after cavernous nerve (CN) injury remains difficult to treat. Calpain plays a critical role in causing neurodegenerative diseases. This study aimed to evaluate whether calpain inhibition preserves erectile function in a rat model of CN injury. Materials and Methods: Rats underwent sham surgery or CN crush injury. The CN-crushed rats were treated with vehicle or MDL-28170, a specific calpain inhibitor. At 1, 2, 3, and 7 days post-surgery, major pelvic ganglia (MPG) were harvested, followed by the measurement of erectile function, respectively. At 28 days, penile tissue and distal CN were harvested, followed by the measurement of erectile function in rats. Calpain activity in MPG and corpus cavernosum, as well as TGF-β1/Smad2 and collagen content in corpus cavernosum, were measured by western blot. Neuronal nitric oxide synthase (nNOS) was observed by immunohistochemistry. Results: Increased calpain activity was observed in MPG and corpus cavernosum. CN crush markedly attenuated the erectile responses and nNOS expression in CN, and these were improved by MDL-28170 treatment. Furthermore, treatment prevented increased TGF-β1/Smad2 and collagen expression in corpus cavernosum. Conclusions: Our results suggested that calpain activation plays a role in pathogenesis of CN injury-associated ED. Calpain inhibition could be a novel approach for preventing the development of ED following CN injury.

Calpain inhibition improves erectile function in diabetic mice via upregulating endothelial nitric oxide synthase expression and reducing apoptosis

“…A previous study showed that calpain inhibition by the calpain inhibitor MDL28170 could preserve the erectile response and neuronal nitric oxide synthase expression in rats suffering from cavernous nerve injury. 20 However, whether calpain inhibition can ameliorate diabetic ED has not yet been studied. In the present study, we used a diabetic model of mice induced with streptozotocin to investigate the effect of calpain inhibition on diabetic ED and explore the possible underlying mechanism.…”

G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes

“…Intracavernous pressure (ICP) and mean arterial blood pressure (MAP) were measured as previously described in our experiment 26. Electrostimulation of the cavernous nerve (CN) was applied as voltage response to stimulation (2.5 V, 5V, and 7.5 V) at 15 Hz with a pulse width of 0.5 ms for 50 s. Three stimulations were conducted at each side of the CN.…”

“…As described previously,2627 briefly, 40 μg of total protein was transferred onto a nitrocellulose membrane (Pierce, Rocford, IL, USA) and incubated with appropriate dilutions of the primary specific antibody, including anti-Akt, anti-phospho-Akt (Thr308), anti-phospho-Akt (Ser473), anti-eNOS, anti-phospho-eNOS (Thr495), anti-phospho-eNOS (Ser1177) (1:1000, CST, Danvers, MA, USA), anti-GRK2, anti-gp91 phox , anti-caspase-3, anti-active (cleaved) caspase-3 antibody (1:1000, Abcam, Cambridge, MA, USA), followed by incubation with horseradish peroxidase (HRP) conjugated secondary antibody. The membranes were then analyzed using a chemiluminescence detection system.…”

An update on the current status and future prospects of erectile dysfunction following radical prostatectomy

“…Therefore, minimizing oxidative stress can be a feasible approach to CN recovery. Also, it was found that calpain, a calcium‐dependent, non‐lysosomal neutral cysteine endopeptidase, and its activation have a role in the pathogenesis of CNI related ED 33 . Calpain inhibition improved erectile responses and neuronal NOS (nNOS) expression with a decrease in TGF‐β1 and collagen expression in penile tissue from CNI rats 33 .…”

“…Also, it was found that calpain, a calcium‐dependent, non‐lysosomal neutral cysteine endopeptidase, and its activation have a role in the pathogenesis of CNI related ED 33 . Calpain inhibition improved erectile responses and neuronal NOS (nNOS) expression with a decrease in TGF‐β1 and collagen expression in penile tissue from CNI rats 33 . The inhibition of calpain could be a choice among the new approaches to prevent the development of ED after CNI 33 .…”