title: Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides.
abstract: Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man.
authors.affiliation: Department of Urology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Calenda
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Tong
authors.forename: Nirmala D
authors.initials: ND
authors.lastname: Kanika
authors.forename: Moses T
authors.initials: MT
authors.lastname: Tar
authors.forename: Sylvia O
authors.initials: SO
authors.lastname: Suadicani
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhang
authors.forename: Arnold
authors.initials: A
authors.lastname: Melman
authors.forename: Catherine
authors.initials: C
authors.lastname: Rougeot
authors.forename: Kelvin P
authors.initials: KP
authors.lastname: Davies
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000473:pathology; D018014:Gene Transfer Techniques; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012471:Salivary Proteins and Peptides / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D012471:Salivary Proteins and Peptides; C517879:glutaminyl-arginyl-phenylalanyl-seryl-arginine; D020098:Natriuretic Peptide, C-Type; D001920:Bradykinin; D002118:Calcium