Abnormal protein expression in the corpus cavernosum impairs erectile function in type 2 diabetes

Abstract

they were then compared with rats that received a normal diet (ND). RESULTSHyperglycaemia and dyslipidaemia were induced in HFD + STZ rats, suggesting that T2D was established. The rats with T2D had associated ED, as both nonadrenergic noncholinergic-mediated corporal relaxation and increased ICP by cavernous nerve stimulation were significantly attenuated compared to the ND group. Western blot analysis revealed diabetes-associated lower expression of endothelial and neuronal nitric oxide synthase (e and nNOS), and cGMPdependent protein kinase (PKG)-1 α / β expression in penile tissue than in the ND group. Contrary to the proteins that regulate corporal relaxation, there were relatively high levels of RhoA/Rho kinase receptor 1 (ROCK1) and ET-A receptor (ETAR) in T2D rats. However, the expressed level of phosphodiesterase-5 and insulin-like growth factor binding protein 3 was not altered significantly in response to T2D. CONCLUSIONDecreased expression of certain proteins that mediate the relaxant mechanism, associated with increased expression of certain proteins that mediate contractile mechanisms, might be important in the development of T2D-associated ED. In particular, down-regulated eNOS/nNOS/ PKG1 as well as up-regulated ETAR/RhoA/ ROCK1 might participate in the aetiology of ED in T2D. KEYWORDS

Yidiyin, a Chinese Herbal Decoction, Improves Erectile Dysfunction in Diabetic Patients and Rats through the NO-cGMP Pathway

“…A growing body of evidence indicates that the erectile tissue of diabetic men and experimental type 1 and 2 diabetes animals manifests an inability to relax in response to the activation of nerves or the endothelium. 10,31,34,35) It is well known that normal erectile function is a hemodynamic neurovascular process involving relaxation of the corpus cavernosum. Although several vasodilators have been implicated in the erectile response, including vasoactive intestinal peptides, prostaglandin, and acetylcholine, the principal neurotransmitter for penile erection is NO, which is produced by the endothelium of the arteries of the penis and nitrergic neurons with the help of endothelial and neuronal NOS in response to sexual stimulation.…”

“…5,7) Increasing evidence also indicates that diabetic ED also results from downregulation of the NO-cGMP signaling in the corpora cavernosum, including impaired NOS activity, low levels of NO and cGMP, and deficient activity of cGMP-dependent kinase. [8][9][10] It is a remedy for diabetic ED to preserve or strengthen the activity of the NO-cGMP pathway. At present, inhibitors of phosphodiesterase type 5 (PDE5) are the most effective oral drugs.…”

The promise of inhibition of smooth muscle tone as a treatment for erectile dysfunction: where are we now?

“…As the downstream signaling of both NE and ET, RhoA/ROCK axis was found to be upregulated in diabetic animals as well. The expression of ROCK1, but not ROCK2, was significantly increased in penile tissues from different diabetic animal models, 4,83,84 indicating that ROCK1 is involved in diabetic ED. Furthermore, Angulo et al 101 demonstrated that diabetes causes hypercontractility of human cavernous tissue by a mechanism involving overactivity of PKC.…”

“…84 Sullivan et al 26 reported a significant increase in ET B receptor binding sites in cavernous tissue of diabetic rabbits. As the downstream signaling of both NE and ET, RhoA/ROCK axis was found to be upregulated in diabetic animals as well.…”

“…However, several studies indicate that the expression of ROCK1, rather than ROCK2, was significantly increased in penile tissues from different diabetic animal models. 4,83,84 In rabbits with bladder outlet obstruction, Chang et al 80 found that the expression of both isoforms of ROCK in the CC is increased. The etiology-dependent changes in the expression of ROCK1 and ROCK2 indicate that they might play different roles in the pathophysiology of ED, which may have implications in the development of therapeutic options.…”