Abstract 052: Direct Correlation Between Blood Pressure and Nephron Endowment in a Genetic Mouse Model of Hypertension

Abstract

Blood pressure high (BPH2) mice represent a novel genetic mouse model of hypertension that was derived from an 8-way cross of common inbred strains of mice. Mice derived from the original cross were segregated by blood pressure and then inbred to establish distinct mouse lines including the BPH2 line, a normotensive genetic control (blood pressure normal; BPN3) as well as a blood pressure low (BPL1) line. The goal of the present study was to test the hypothesis that the level of blood pressure in BPH2, BPN3, BPL1, and C57Bl/6 (normotensive inbred control) mice correlates with nephron endowment. Systolic blood pressure (SBP) was measured in male BPH2, BPN3, BPL1, and C57BL/6 mice (n=6/group) using tail-cuff plethysmography. SBP in BPH2, BPN3, BPL1, and C57BL/6 mice averaged 152±2, 117±1; 105±4; and 107±3 mm Hg, respectively. SBP was significantly greater (P<0.05) in BPH2 mice compared to the other three groups of mice. In contrast, SBP was found to be similar (P>0.05) between BPL1 and C57BL/6 mice and significantly (P<0.05) lower than that in either BPH2 or BPN3 mice. Total kidney weight/body weight ratios were found to be similar (P>0.05) in BPH2 and BPN3 mice and significantly (P<0.05) higher than that in BPL1 and C57BL/6 mice. Nephron number as assessed by the acid maceration technique revealed that total nephron number in BPH2, BPN3, BPL1, and C57Bl/6 averaged 10,409±285, 25,333±478, 27,300±445 and 22,533±668 nephrons per kidney, respectively. There was an extremely significant correlation (R2=0.779; P<0.0001) between nephron number and systolic blood pressure. These data provide evidence that blood pressure in a genetic mouse model of hypertension correlates with total nephron number. These findings are consistent with the emerging concept that nephron endowment at birth or progressive loss of nephrons with age or disease directly impacts blood pressure. Thus, we suggest that the BPH2 mouse can serve as an important experimental model to investigate the intrinsic relationship between nephron endowment and blood pressure.