Myogenic Responses of Mouse Isolated Perfused Renal Afferent Arterioles Effects of Salt Intake and Reduced Renal Mass En Yin Lai, Maristela L. Onozato, Glenn Solis, Shakil Aslam, William J. Welch, Christopher S. Wilcox Abstract—Because defects in renal autoregulation may contribute to renal barotrauma in chronic kidney disease, we tested the hypothesis that the myogenic response is diminished by reduced renal mass. Kidneys from 5/6 nephrectomized mice had only a minor increase in the glomerular sclerosis index. The telemetric mean arterial pressure (10810 mm Hg) was unaffected after 3 months of high-salt intake (6% salt in chow) or reduced renal mass. Afferent arterioles from 5/6 nephrectomized mice and sham-operated controls were perfused ex vivo during step changes in pressure from 40 to 134 mm Hg. Afferent arterioles developed a constriction and a linear increase in active wall tension above a perfusion pressure of 366 mm Hg, without a plateau. The slope of active wall tension versus perfusion pressure defined the myogenic response, which was similar in sham mice fed normal or high-salt diets for 3 months (2.900.22 versus 3.220.40 dynes  cm -1 /mm Hg; P value not significant). The myogenic response was unaffected after 3 days of reduced renal mass on either salt diet (3.390.61 versus 4.040.47 dynes  cm -1 /mm Hg) but was reduced (P0.05) in afferent arterioles from reduced renal mass groups fed normal and high salt at 3 months (2.100.28 and 1.350.21 dynes  cm -1 /mm Hg). In conclusion, mouse renal afferent arterioles develop a linear increase in myogenic tone around the range of ambient perfusion pressures. This myogenic response is impaired substantially in the mouse model of prolonged reduced renal mass, especially during high salt intake. (Hypertension. 2010;55:983-989.) Key Words: kidney  renal autoregulation  chronic kidney disease  hypertension  salt sensitivity R enal autoregulation implies a proportionate increase in renal vascular resistance with increasing perfusion pres- sure. Autoregulation is mediated predominantly by myogenic and tubuloglomerular feedback (TGF) components. Loutzen- hiser and colleagues 1,2 demonstrated a myogenic response in the renal afferent arteriole of hydronephrotic kidneys from rats that contributed 31% to the autoregulation of renal blood flow. 3 Takenaka et al 4 reported a one-third decrease in afferent arteriolar diameter and a maintained blood flow velocity in juxtamedullary nephrons of the rat during in- creases in renal perfusion pressure. Impaired autoregulation and systemic hypertension in chronic kidney disease (CKD) have been proposed to cause the elevated glomerular capil- lary pressure that has been linked to progressive glomerular injury. 5 Dietary salt restriction reduced glomerulosclerosis and renal damage in rats with reduced renal mass (RRM) 6,7 and reduced proteinuria in patients with CKD. 8 A preliminary study reported that a high salt intake impaired autoregulation of the juxtamedullary afferent arterioles in the rat. 9 However, the myogenic response of isolated afferent arterioles has not been studied in models of CKD or during changes in salt intake. Renal afferent arterioles are the main renal resistance vessels and, unlike the arcuate or interlobular arteries, 10 can have strong myogenic contractions. 11,12 We tested the hypoth- esis that the myogenic responses of renal cortical afferent arterioles were impaired by prolonged RRM and by dietary salt loading. The aim was to study the myogenic responses in isolated perfused afferent arterioles where the perfusion pressure could be controlled and changes in the luminal diameter measured directly without confounding effects of the TGF or circulating factors. We evaluated myogenic responses at 3 days, 3 weeks, and 3 months after RRM or sham operations during normal or high levels of dietary salt intake. Methods and Protocols Male C57BL6 mice weighing 22 to 30 g (Jackson Laboratory, Bar Harbor, ME) were fed a 0.4% NaCl control-test diet (normal salt [NS]; Harlan Teklad) or an equivalent 6% NaCl diet (high salt [HS]; TD92055, Harlan Teklad) and allowed free access to tap water. All of the procedures conformed to the Guide for Care and Use of Laboratory Animals prepared by the Institute for Laboratory Animal Research. Studies were approved by the Georgetown University Animal Care and Use Committee. Received December 14, 2009; first decision December 31, 2009; revision accepted February 1, 2010. From the Division of Nephrology and Hypertension and Hypertension, Kidney, and Vascular Health Center, Georgetown University, Washington, DC. Correspondence to Christopher S. Wilcox, Division of Nephrology and Hypertension, Georgetown University Medical Center, 3800 Reservoir Rd, NW, 6 PHC Building, F6003, Washington, DC 20007. E-mail wilcoxch@georgetown.edu © 2010 American Heart Association, Inc. Hypertension is available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.109.149120 983 by guest on April 1, 2017 http://hyper.ahajournals.org/ Downloaded from