title: Altered myogenic vasoconstriction and regulation of whole kidney blood flow in the ASIC2 knockout mouse.
abstract: Previous studies from our laboratory have suggested that degenerin proteins contribute to myogenic constriction, a mechanism of blood flow regulation and protection against pressure-dependent organ injury, in renal vessels. The goal of the present study was to determine the importance of one family member, acid-sensing ion channel 2 (ASIC2), in myogenic constriction of renal interlobar arteries, myogenic regulation of whole kidney blood flow, renal injury, and blood pressure using ASIC2(+/+), ASIC2(+/-), and ASIC2(-/-) mice. Myogenic constriction in renal interlobar arteries was impaired in ASIC2(+/-) and ASIC2(-/-) mice, whereas constriction to KCl/phenylephrine was unchanged. Correction of whole kidney renal vascular resistance (RVR) during the first 5 s after a 10- to 20-mmHg step increase in perfusion pressure, a timeframe associated with myogenic-mediated correction of RVR, was slowed (4.2 ± 0.9, 0.3 ± 0.7, and 2.4 ± 0.3 resistance units/s in ASIC2(+/+), ASIC2(+/-), and ASIC2(-/-) mice). Although modest reductions in function were observed in ASIC2(-/-) mice, greater reductions were observed in ASIC2(+/-) mice, which may be explained by protein-protein interactions of ASIC2 with other degenerins. Isolated glomeruli from ASIC2(+/-) and ASIC2(-/-) mice had modest alterations in the expression of inflammation and injury markers (transforming growth factor-β, mouse anti-target of antiproliferative antibody-1, and nephrin), whereas ASIC2(+/-) mice had an increase in the remodeling marker collagen type III. Consistent with a more severe loss of function, mean arterial pressure was increased in ASIC2(+/-) mice (131 ± 3 mmHg) but not in ASIC2(-/-) mice (122 ± 3 vs. 117 ± 2 mmHg in ASIC2(+/+) mice). These results suggest that ASIC2 contributes to transduction of the renal myogenic response and are consistent with the protective role of myogenic constriction against renal injury and hypertension.
authors.affiliation: Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Kimberly P
authors.initials: KP
authors.lastname: Gannon
authors.affiliation: Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Susan E
authors.initials: SE
authors.lastname: McKey
authors.affiliation: Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: David E
authors.initials: DE
authors.lastname: Stec
authors.affiliation: Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi hdrummond@umc.edu.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Drummond
mesh_terms: D062565:Acid Sensing Ion Channels / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D062186:Arterial Pressure; D015415:Biomarkers / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000098:blood supply*; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D040542:Mechanotransduction, Cellular; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010641:Phenotype; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels; D015415:Biomarkers; D024061:Collagen Type III; D018836:Inflammation Mediators; D014662:Vasoconstrictor Agents
keywords: acid-sensing ion channel 2; degenerin; pressure-induced constriction; renal injury