Abstract P247: Elastin Insufficiency Impairs Renal Hemodynamics And Accelerates Aging-associated Structural And Functional Remodeling Of Preglomerular Arterioles

Abstract

Elastin degradation and fragmentation are hallmarks of arterial stiffness and renal dysfunction associated with aging. However, it is unclear whether elastin insufficiency contributes to the changes in the structure and function of the resistance vasculature of the kidney during aging. Here we determined how increased vascular stiffness due to elastin insufficiency alters renal hemodynamics and mechanical properties of preglomerular arterioles. We assessed renal hemodynamics under anesthesia in 14-16-month-old female wild type (WT) and elastin heterozygous ( Eln +/- ) mice. Renal autoregulation was assessed by a stepwise increase in renal perfusion pressure (RPP) by simultaneously occluding the superior mesenteric and celiac arteries. Myogenic constriction and arterial stiffness were assessed by pressure myography of isolated renal interlobar arteries. Baseline renal vascular resistance (RVR) was elevated in Eln +/- mice (13.8 ± 2.9 vs 11.2 ± 1.4 mmHg/μL/min/g left kidney weight), while systolic blood pressure (SBP; 75.1 ± 7.4 vs 91 ± 4.2mmHg), renal blood flow (RBF; 6.3 ± 1.2 vs 7.4 ± 1.7 μL/min/g left kidney weight), renal plasma flow (RPF; 3.4 ± 0.8 vs 5 ± 1.2 mL/min/g/ left kidney weight) and urine flow rate, all trended lower in Eln +/- mice compared to WT mice. Glomerular filtration rate (GFR) and filtration fraction (FF) were similar between the two groups. A stepwise increase in RPP caused a slower decline and rise in RBF and RVR, respectively, in Eln +/- relative to WT mice. The maximal changes in RBF (5 ± 1.1 vs 4.7 ± 0.8 μL/min/g left kidney weight), RVR (17.6 ± 7.3 vs 22.5 ± 2.1 mmHg/μL/min/g left kidney weight), urine flow rate,GFR, and FF were less robust in Eln +/- mice. RPF decreased in WT mice in response to raising RPP, whereas it remained unchanged in Eln +/- mice. Myogenic response and increases in elastic modulus and wall tension following stepwise changes in intraluminal pressure were all augmented in interlobar arteries from Eln +/- relative to WT mice. However, there was no difference in kidney weight/tibia length ratio between the two genotypes. We conclude that elastin insufficiency impairs renal hemodynamics by exacerbating age associated increase in vascular stiffness.