title: Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure.
abstract: Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing ofDrd2using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue ofDrd2expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vector withDRD2. RenalDrd2siRNA treatment decreased the renal expression of DRD2 protein by 55%, andDRD2AAV treatment increased the renal expression of DRD2 protein by 7.5- to 10-fold. Renal-selectiveDRD2rescue reduced the expression of proinflammatory factors and kidney injury, preserved renal function, and normalized systolic and diastolic blood pressure. These results demonstrate that the deleterious effects of renal-selectiveDrd2silencing on renal function and blood pressure were rescued by renal-selective overexpression ofDRD2. Moreover, the deleterious effects of 45-minute bilateral ischemia/reperfusion on renal function and blood pressure in mice were ameliorated by a renal-selective increase in DRD2 expression by the retrograde ureteral infusion ofDRD2AAV immediately after the induction of ischemia/reperfusion injury. Thus, 14 days after ischemia/reperfusion injury, the renal expression of profibrotic factors, serum creatinine, and blood pressure were lower in mice infused withDRD2AAV than in those infused with control AAV. These results indicate an important role of renal DRD2 in limiting renal injury and preserving normal renal function and blood pressure.
authors.affiliation: Department of Medicine, The George Washington University, Washington, DC, USA, and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Prasad R
authors.initials: PR
authors.lastname: Konkalmatt
authors.affiliation: Department of Medicine, The George Washington University, Washington, DC, USA, and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Maryland Medical Center, Baltimore, Maryland, USA.
authors.forename: Cinthia
authors.initials: C
authors.lastname: Drachenberg
authors.affiliation: Department of Medicine, The George Washington University, Washington, DC, USA, and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Medicine, The George Washington University, Washington, DC, USA, and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA; Department of Physiology, The George Washington University, Washington, DC, USA, and University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: Department of Medicine, The George Washington University, Washington, DC, USA, and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ines
authors.initials: I
authors.lastname: Armando