Vascular remodeling in arteriovenous fistula treated with PDE5A inhibitors
Abstract The arteriovenous fistula (AVF) is the lifeline for hemodialysis patients. However, there are currently no effective therapies promoting AVF maturation. AVF dilation by smooth muscle cell relaxation, through increased cyclic guanosine monophosphate (cGMP), is one potential mechanism to impr...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70331 |
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| author | Maheshika Somarathna Hannah Northrup Kevin Ingle Tatyana Isayeva‐Waldrop Nguyen Thuy Nhu Nguyen Bailey Lose Yan‐Ting Shiu Timmy Lee |
| author_facet | Maheshika Somarathna Hannah Northrup Kevin Ingle Tatyana Isayeva‐Waldrop Nguyen Thuy Nhu Nguyen Bailey Lose Yan‐Ting Shiu Timmy Lee |
| author_sort | Maheshika Somarathna |
| collection | DOAJ |
| description | Abstract The arteriovenous fistula (AVF) is the lifeline for hemodialysis patients. However, there are currently no effective therapies promoting AVF maturation. AVF dilation by smooth muscle cell relaxation, through increased cyclic guanosine monophosphate (cGMP), is one potential mechanism to improve AVF remodeling. In this study, we examined the cGMP pathway and its inhibitor phosphodiesterase 5A (PDE5A) in rat, pig, and human AVF. We administered the PDE5A inhibitor, sildenafil, to rats with femoral AVFs and analyzed AVF histological and hemodynamic parameters. We observed that AVF creation increases PDE5A expression in rodent and porcine AVF models. Similarly, we observed an increase in PDE5A expression in the anastomotic regions of AVFs from hemodialysis patients when compared to pre‐AVF placement. Sildenafil‐treated rats showed significantly increased ultrasound‐derived AVF volumetric blood flow and increased MRI‐derived 3‐dimensional lumen diameter when compared to controls. MRI‐based computational fluid dynamics showed that sildenafil‐treated rats had increased anastomotic hemodynamics compared to control rats. Histology showed similar intimal hyperplasia in sildenafil‐treated and control rats. In conclusion, sildenafil treatment increases AVF vein outward expansion and blood flow without affecting the level of intimal hyperplasia. PDE5A inhibitors serve as a potential therapeutic approach to promote AVF maturation by enhancing outward vascular remodeling. |
| format | Article |
| id | doaj-art-1ca344d234a74ede9ee690dc55cc674f |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-1ca344d234a74ede9ee690dc55cc674f2025-08-20T03:49:44ZengWileyPhysiological Reports2051-817X2025-05-01139n/an/a10.14814/phy2.70331Vascular remodeling in arteriovenous fistula treated with PDE5A inhibitorsMaheshika Somarathna0Hannah Northrup1Kevin Ingle2Tatyana Isayeva‐Waldrop3Nguyen Thuy Nhu Nguyen4Bailey Lose5Yan‐Ting Shiu6Timmy Lee7Department of Medicine and Division of Nephrology University of Alabama at Birmingham Birmingham Alabama USADepartment of Internal Medicine and Division of Nephrology and Hypertension University of Utah Salt Lake Utah USADepartment of Medicine and Division of Nephrology University of Alabama at Birmingham Birmingham Alabama USADepartment of Medicine and Division of Nephrology University of Alabama at Birmingham Birmingham Alabama USADepartment of Medicine and Division of Nephrology University of Alabama at Birmingham Birmingham Alabama USADepartment of Medicine and Division of Nephrology University of Alabama at Birmingham Birmingham Alabama USADepartment of Internal Medicine and Division of Nephrology and Hypertension University of Utah Salt Lake Utah USADepartment of Medicine and Division of Nephrology University of Alabama at Birmingham Birmingham Alabama USAAbstract The arteriovenous fistula (AVF) is the lifeline for hemodialysis patients. However, there are currently no effective therapies promoting AVF maturation. AVF dilation by smooth muscle cell relaxation, through increased cyclic guanosine monophosphate (cGMP), is one potential mechanism to improve AVF remodeling. In this study, we examined the cGMP pathway and its inhibitor phosphodiesterase 5A (PDE5A) in rat, pig, and human AVF. We administered the PDE5A inhibitor, sildenafil, to rats with femoral AVFs and analyzed AVF histological and hemodynamic parameters. We observed that AVF creation increases PDE5A expression in rodent and porcine AVF models. Similarly, we observed an increase in PDE5A expression in the anastomotic regions of AVFs from hemodialysis patients when compared to pre‐AVF placement. Sildenafil‐treated rats showed significantly increased ultrasound‐derived AVF volumetric blood flow and increased MRI‐derived 3‐dimensional lumen diameter when compared to controls. MRI‐based computational fluid dynamics showed that sildenafil‐treated rats had increased anastomotic hemodynamics compared to control rats. Histology showed similar intimal hyperplasia in sildenafil‐treated and control rats. In conclusion, sildenafil treatment increases AVF vein outward expansion and blood flow without affecting the level of intimal hyperplasia. PDE5A inhibitors serve as a potential therapeutic approach to promote AVF maturation by enhancing outward vascular remodeling.https://doi.org/10.14814/phy2.70331arteriovenous fistulahemodialysisPDE5Asildenafilvascular accessvascular remodeling |
| spellingShingle | Maheshika Somarathna Hannah Northrup Kevin Ingle Tatyana Isayeva‐Waldrop Nguyen Thuy Nhu Nguyen Bailey Lose Yan‐Ting Shiu Timmy Lee Vascular remodeling in arteriovenous fistula treated with PDE5A inhibitors Physiological Reports arteriovenous fistula hemodialysis PDE5A sildenafil vascular access vascular remodeling |
| title | Vascular remodeling in arteriovenous fistula treated with PDE5A inhibitors |
| title_full | Vascular remodeling in arteriovenous fistula treated with PDE5A inhibitors |
| title_fullStr | Vascular remodeling in arteriovenous fistula treated with PDE5A inhibitors |
| title_full_unstemmed | Vascular remodeling in arteriovenous fistula treated with PDE5A inhibitors |
| title_short | Vascular remodeling in arteriovenous fistula treated with PDE5A inhibitors |
| title_sort | vascular remodeling in arteriovenous fistula treated with pde5a inhibitors |
| topic | arteriovenous fistula hemodialysis PDE5A sildenafil vascular access vascular remodeling |
| url | https://doi.org/10.14814/phy2.70331 |
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