title: Angiotensin-(1-7) Downregulates Diabetes-Induced cGMP Phosphodiesterase Activation in Rat Corpus Cavernosum.
abstract: Molecular mechanisms of the beneficial effects of angiotensin-(1-7), Ang-(1-7), in diabetes-related complications, including erectile dysfunction, remain unclear. We examined the effect of diabetes and/or Ang-(1-7) treatment on vascular reactivity and cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE) in corpus cavernosum. Male Wistar rats were grouped as (1) control, (2) diabetic (streptozotocin, STZ, treated), (3) control + Ang-(1-7), and (4) diabetic + Ang-(1-7). Following 3 weeks of Ang-(1-7) treatment subsequent to induction of diabetes, rats were sacrificed. Penile cavernosal tissue was isolated to measure vascular reactivity, PDE gene expression and activity, and levels of p38MAP kinase, nitrites, and cGMP. Carbachol-induced vasorelaxant response after preincubation of corpus cavernosum with PE was significantly attenuated in diabetic rats, and Ang-(1-7) markedly corrected the diabetes-induced impairment. Gene expression and activity of PDE and p38MAP kinase were significantly increased in cavernosal tissue of diabetic rats, and Ang-(1-7) markedly attenuated STZ-induced effects. Ang-(1-7) significantly increased the levels of nitrite and cGMP in cavernosal tissue of control and diabetic rats. Cavernosal tissue of diabetic rats had significantly reduced cGMP levels and Ang-(1-7) markedly prevented the STZ-induced cGMP depletion. This study demonstrates that attenuation of diabetes-induced PDE activity might be one of the key mechanisms in the beneficial effects of Ang-(1-7).
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
authors.forename: Gursev S
authors.identifier: 0000-0003-3496-8661
authors.initials: GS
authors.lastname: Dhaunsi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
authors.forename: Mariam
authors.identifier: 0000-0002-6464-031X
authors.initials: M
authors.lastname: Yousif
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
authors.forename: Batoul
authors.identifier: 0000-0002-8675-8941
authors.initials: B
authors.lastname: Makki
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
authors.forename: Saghir
authors.identifier: 0000-0003-3177-946X
authors.initials: S
authors.lastname: Akhtar
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
authors.forename: Ibrahim F
authors.initials: IF
authors.lastname: Benter
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015536:Down-Regulation; D007172:Erectile Dysfunction / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D009573:Nitrites / Q000737:chemistry; D010413:Penis / Q000098:blood supply* / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D009573:Nitrites; D010446:Peptide Fragments; D000803:Angiotensin I; D048051:p38 Mitogen-Activated Protein Kinases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP; C118790:angiotensin I (1-7)