| First Author | Gannon KP | Year | 2015 |
| Journal | Am J Physiol Renal Physiol | Volume | 308 |
| Issue | 4 | Pages | F339-48 |
| PubMed ID | 25520010 | Mgi Jnum | J:237550 |
| Mgi Id | MGI:5812877 | Doi | 10.1152/ajprenal.00572.2014 |
| Citation | Gannon KP, et al. (2015) Altered myogenic vasoconstriction and regulation of whole kidney blood flow in the ASIC2 knockout mouse. Am J Physiol Renal Physiol 308(4):F339-48 |
| abstractText | 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-beta, 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. |
