Renal dopaminergic defect in C57Bl/6J mice

Abstract

The C57Bl/6J mouse strain, the genetic background of many transgenic and gene knockout models, is salt sensitive and resistant to renal injury. We tested the hypothesis that renal dopaminergic function is defective in C57Bl/6J mice. On normal NaCl (0.8%, 1 wk) diet, anesthetized and conscious (telemetry) blood pressures were similar in C57Bl/6J and SJL/J mice. High NaCl (6%, 1 wk) increased blood pressure (approximately 30%) in C57Bl/6J but not in SJL/J mice and urinary dopamine to greater extent in SJL/J than in C57Bl/6J mice. Absolute and fractional sodium excretions were lower in SJL/J than in C57Bl/6J mice. The blood pressure-natriuresis plot was shifted to the right in C57Bl/6J mice. Renal expressions of D(1)-like (D(1)R and D(5)R) and angiotensin II AT(1) receptors were similar on normal salt, but high salt increased D(5)R only in C57Bl/6J. GRK4 expression was lower on normal but higher on high salt in C57Bl/6J than in SJL/J mice. Salt increased the excretion of microalbumin and 8-isoprostane (oxidative stress marker) and the degree of renal injury to a greater extent in SJL/J than in C57Bl/6J mice. A D(1)-like receptor agonist increased sodium excretion whereas a D(1)-like receptor antagonist decreased sodium excretion in SJL/J but not in C57Bl/6J mice. In contrast, parathyroid hormone had a similar natriuretic effect in both strains. These results show that defective D(1)-like receptor function is a major cause of salt sensitivity in C57Bl/6J mice, decreased renal dopamine production might also contribute. The relative resistance to renal injury of C57Bl/6J may be a consequence of decreased production of reactive oxygen species.

Deletion of cyclooxygenase-2 in the mouse increases arterial blood pressure with no impairment in renal NO production in response to chronic high salt intake

“…wild-type C57BL6 mice, as observed previously (6), and as observed in mice with disruption of eNOS, COX-1, IP, and EP2 receptors, and mPGES-1 Ϫ/Ϫ (7,14,17,19). IP, EP2, and EP4 receptors are Gs-coupled adenylyl cyclase-activating receptors associated with the vasa recta, the medullary collecting ducts, and the descending limb of the loop of Henle.…”

Role of GRK4 in the Regulation of Arterial AT1 Receptor in Hypertension

“…In the current study, the transgenic mice are on 50% C57BL/6 Jackson and 50% SJL Jackson mouse background. GRK4 and AT 1 R protein expression are greater in C57BL/6 Jackson than SJL Jackson mice 41 . hGRK4γ 142V transgenic mice on C57BL/6 background are also hypertensive that is caused in part by decreased renal D 1 receptor function 11,13,34 and increased renal AT 1 R expression 34 .…”

“…To further investigate the role of GRK4 variants on the hypertension, we generated hGRK4γ 142V and GRK4γ WT transgenic mice on C57BL/6J and SJL/J background. C57BL/6 mice are salt-sensitive while SJL/J mice are saltresistant 41 . We now report that hGRK4γ 142V mice on mixed C57BL/6J and SJL/J background have increased blood pressure.…”

Sorting Nexin 1 Loss Results in D5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice

“…Infusion of vehicle or non-silencing mock siRNA (Qiagen) served as controls. The systolic and diastolic blood pressure were measured (Cardiomax II) from the aorta via the femoral artery (12,33) before and after the 7-day siRNA infusion. At the end of the study, the siRNA-transfected kidney was removed before the mice were euthanized via a lethal dose of CO 2 by inhalation followed by decapitation to confirm death while still under anesthesia.…”