INTRODUCTION: Erectile dysfunction (ED) afflicts 50% of diabetic men, many of whom experience poor results with phosphodiesterase type 5 inhibitors. The protein tyrosine kinase (PTK) inhibitor imatinib (Gleevec, Novartis Pharmaceuticals, Basel, Switzerland) has therapeutic potential in diabetic men by maintaining β-cell function. AIM: To determine if imatinib has a beneficial effect on erectile and vascular function in diabetic rats. METHODS: Male Sprague-Dawley rats were divided into six groups: (i) control; (ii) imatinib (50mg/kg, daily gavage)-treated control; (iii) diabetic; (iv) preventive imatinib (8 weeks); (v) reversal imatinib (4 weeks untreated diabetes and 4 weeks of treatment); and (vi) insulin (8 weeks)-treated diabetic rats. MAIN OUTCOME MEASURES: After 8 weeks, all groups underwent cavernosal nerve stimulation and measurements of intracavernosal pressure (ICP) and mean arterial pressure (MAP). Contractile and relaxation responses were evaluated using isolated strips of corpus cavernosum smooth muscle (CCSM) and aorta. RESULTS: Diabetic rats exhibited a 32% decrease in weight and fivefold increase in blood glucose levels. Imatinib-treated diabetic rats gained weight and partially improved blood glucose levels. Diabetic rats displayed a decrease in ICP/MAP. While maximum electrical field stimulation- and acetylcholine (ACh)-induced relaxations in CCSM strips from the diabetics were reduced, preventive imatinib or insulin treatment normalized ICP/MAP ratios and improved relaxation responses. ACh responses in diabetic aortas were diminished by 50.1% and restored by imatinib. While contractile responses to phenylephrine in diabetic CCSM were not altered, there was a significant enhancement (59.4 %) in the aortic contractile response in diabetic rats, which was restored by imatinib and insulin treatment. CONCLUSIONS: In diabetic rats, prolonged therapy with imatinib improves diabetes-related ED and vascular function, which may involve normalization of high glucose levels and restoration of PTK activation. Future studies are needed to elaborate on the actions of imatinib on diabetic vascular complications.
INTRODUCTION:Erectile dysfunction (ED) afflicts 50% of diabeticmen, many of whom experience poor results with phosphodiesterase type 5 inhibitors. The protein tyrosine kinase (PTK) inhibitor imatinib (Gleevec, Novartis Pharmaceuticals, Basel, Switzerland) has therapeutic potential in diabeticmen by maintaining β-cell function. AIM: To determine if imatinib has a beneficial effect on erectile and vascular function in diabeticrats. METHODS: Male Sprague-Dawley rats were divided into six groups: (i) control; (ii) imatinib (50mg/kg, daily gavage)-treated control; (iii) diabetic; (iv) preventive imatinib (8 weeks); (v) reversal imatinib (4 weeks untreated diabetes and 4 weeks of treatment); and (vi) insulin (8 weeks)-treated diabeticrats. MAIN OUTCOME MEASURES: After 8 weeks, all groups underwent cavernosal nerve stimulation and measurements of intracavernosal pressure (ICP) and mean arterial pressure (MAP). Contractile and relaxation responses were evaluated using isolated strips of corpus cavernosum smooth muscle (CCSM) and aorta. RESULTS:Diabeticrats exhibited a 32% decrease in weight and fivefold increase in blood glucose levels. Imatinib-treated diabeticrats gained weight and partially improved blood glucose levels. Diabeticrats displayed a decrease in ICP/MAP. While maximum electrical field stimulation- and acetylcholine (ACh)-induced relaxations in CCSM strips from the diabetics were reduced, preventive imatinib or insulin treatment normalized ICP/MAP ratios and improved relaxation responses. ACh responses in diabetic aortas were diminished by 50.1% and restored by imatinib. While contractile responses to phenylephrine in diabetic CCSM were not altered, there was a significant enhancement (59.4 %) in the aortic contractile response in diabeticrats, which was restored by imatinib and insulin treatment. CONCLUSIONS: In diabeticrats, prolonged therapy with imatinib improves diabetes-related ED and vascular function, which may involve normalization of high glucose levels and restoration of PTK activation. Future studies are needed to elaborate on the actions of imatinib on diabetic vascular complications.
Authors: Edward A Pankey; Supat Thammasiboon; George F Lasker; Syed Baber; Joseph A Lasky; Philip J Kadowitz Journal: Am J Physiol Heart Circ Physiol Date: 2013-08-30 Impact factor: 4.733
Authors: Biljana Musicki; Anthony J Bella; Trinity J Bivalacqua; Kelvin P Davies; Michael E DiSanto; Nestor F Gonzalez-Cadavid; Johanna L Hannan; Noel N Kim; Carol A Podlasek; Christopher J Wingard; Arthur L Burnett Journal: J Sex Med Date: 2015-12-08 Impact factor: 3.802
Authors: D Mokhtari; A Al-Amin; K Turpaev; T Li; O Idevall-Hagren; J Li; A Wuttke; R G Fred; P Ravassard; R Scharfmann; A Tengholm; N Welsh Journal: Diabetologia Date: 2013-03-05 Impact factor: 10.122