Abstract 252: Renal Rescue of D2R Function in Mice Using an AAV9 Vector Reverses the Renal Injury and High Blood Pressure Induced by D2R Silencing in the Kidney
| Autor: | Prasad R Konkalmatt, Laureano D Asico, Yu Yang, Pedro A Jose, Ines Armando |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Hypertension. 64 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hyp.64.suppl_1.252 |
| Popis: | Lack or downregulation of dopamine D2 receptor (D2R) function in mice increases the vulnerability to renal inflammation. Recent studies from our laboratory showed that long-term (28 days) selective down regulation of D2R in one kidney in mice with two intact kidneys increases systolic blood pressure and the expression of inflammatory and injury markers. We hypothesized that rescuing D2R function by re-expressing the receptor in the kidney of mice with D2R silencing will reduce renal inflammation and injury, and normalize blood pressure. To test our hypothesis we silenced D2R expression by the renal subcapsular infusion of D2RsiRNA and then we rescued the silenced D2R expression using retrograde ureteral infusion of AAV9 vector carrying wild-type D2R (D2RAAV). Mice were treated with non-silencing siRNA (NS siRNA) or D2RsiRNA (3 μg/day, n=6 per group) using 28 day osmotic minipumps. Fourteen days following the initiation of siRNA treatment, each group was treated with control AAV (CAAV) or D2RAAV (n=3 per group, 1e+11 viral genome particles per mouse). Fourteen days following AAV administration, blood pressure was recorded and organs were collected. D2R expression was decreased in D2RsiRNA-treated kidneys compared with NS siRNA-treated kidneys (immunoblotting: 54 ± 0.8 vs 100± 22 %; P |
| Databáze: | OpenAIRE |
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