atrial-natriuretic-factor and Erectile-Dysfunction

This study was aimed to analyze the potential role of Corin in the procession of diabetic ED and to explore the underlying mechanism. Diabetic ED rat model was constructed and the characteristics of diabetic ED and control rats were recorded at 4, 8, 12, and 16 weeks. qRT-PCR and Western bloting were used to detected the mRNA and protein levels. Intracellular cGMP detection was accomplished using a commercial radioimmunoassay method. Vascular endothelial cell from rat corpus cavernosum spiral artery was isolated and transfected with si- Corin to analyzed the potential role of Corin. Cell viability was assessed using crystal violet. The results showed that diabetic ED rats showed significantly higher glucose level, and lower body weight, ICP level, and ICP/MAP ratio at 12 and 16 weeks in diabetic ED rats compared with control rats. The protein levels of Corin, atrial natriuretic peptide (ANP) and eNOS, and the level of cGMP were significantly down-regulated in corpus cavernosum in diabetic ED rats, revealing the potential role of Corin in NO-associated diabetic ED. Further, studies proved that defect of Corin not only inhibited the vascular endothelial cell viability in high-glucose condition, but also suppressed ANP, eNOS, and cGMP expression in vascular endothelial cells. To sum up, Corin contributes to the progression of diabetic ED and the underlying mechanism is associated with the down-regulation of ANP /NO/cGMP signal pathway. J. Cell. Biochem. 118: 2325-2332, 2017. © 2017 Wiley Periodicals, Inc.

Topics: Animals; Arterial Pressure; Atrial Natriuretic Factor; Blood Pressure; Cell Survival; Cyclic GMP; Diabetes Mellitus, Experimental; Erectile Dysfunction; Male; Nitrogen Oxides; Rats; Rats, Sprague-Dawley; Serine Endopeptidases

Receptors for natriuretic peptides have been demonstrated as potential targets for the treatment of male erectile dysfunction.. This study investigates the relaxant effects of the atrial natriuretic peptide (ANP) and uroguanylin (UGN), and expression of natriuretic peptide receptors on strips of human corpora cavernosa (HCC).. Quantitative analysis of natriuretic receptor expression and relaxation of precontracted strips were used to assess the membrane-bound guanylate cyclase-cyclic guanosine monophosphate (cGMP) pathway in HCC strips.. HCC was obtained from a cadaver donor at the time of collection of organs for transplantation (14-47 years) and strips were mounted in organ baths for isometric studies.. ANP and UGN both induced concentration-dependent relaxation on HCC strips with a maximal response attained at 300 nM, corresponding to 45.4±4.0% and 49±4.8%, respectively. The relaxation is not affected by 30 µM 1H-[1,2,4]oxaolodiazolo[4,3-a]quinoxalin-1-one (ODQ) (a soluble guanylate cyclase inhibitor), but it is significantly blocked by 10 µM isatin, a nonspecific particulate guanylate cyclase (pGC) inhibitor. UGN was unable to potentiate electrical field stimulation (EFS) or acetylcholine-induced relaxations. The potential role of pGC activation and cGMP generation in this effect is reinforced by the potentiation of this effect by phosphodiesterase-5 inhibitor vardenafil (55.0±7.5-UGN vs. 98.6±1.4%-UGN+vardenafil; P<0.05). The relaxant effect was also partially (37.6%) blocked by the combination iberitoxin-apamin but was insensitive to glybenclamide. The expression of guanylate cyclase receptors (GC-A, GC-B, GC-C) and the expression of the natriuretic peptide "clearance" receptor (NPR-C) were confirmed by real-time polymerase chain reaction. The exposure of HCC strips to ANP (1 µM) and UGN (10 µM) significantly increased cGMP, but not cyclic adenosine monophosphate (cAMP) levels.. UGN relaxes HCC strips by a guanylate cyclase and K(ca)-channel-dependent mechanism. These findings obtained in HCC reveal that the natriuretic peptide receptors are potential targets for the development of new drugs for the treatment of erectile dysfunction.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Cadaver; Cyclic AMP; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Guanylate Cyclase; Humans; Male; Middle Aged; Muscle Relaxation; Muscle, Smooth; Natriuretic Peptides; Penis; Receptors, Atrial Natriuretic Factor; Receptors, Cytoplasmic and Nuclear; Receptors, Peptide; Soluble Guanylyl Cyclase; Young Adult