| First Author | Li J | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 304 |
| Issue | 7 | Pages | F1000-8 |
| PubMed ID | 23389451 | Mgi Jnum | J:195418 |
| Mgi Id | MGI:5484458 | Doi | 10.1152/ajprenal.00434.2012 |
| Citation | Li J, et al. (2013) Renal protective effects of alpha-calcitonin gene-related peptide in deoxycorticosterone-salt hypertension. Am J Physiol Renal Physiol 304(7):F1000-8 |
| abstractText | Deoxycorticosterone salt (DOC-salt) hypertension-induced renal damage is enhanced in alpha-calcitonin gene-related peptide (alpha-CGRP) knockout (KO) compared with wild-type (WT) mice. However, since the alpha-CGRP KO mice have a 15-20 mmHg higher baseline mean arterial pressure (MAP) than WT mice, they also have a higher MAP than WT mice throughout the course of DOC-salt hypertension. To determine the mechanism by which the absence of alpha-CGRP enhances hypertension-induced renal damage, DOC-salt hypertension was induced in telemetry probe implanted alpha-CGRP KO and WT mice. To equalize the blood pressure (BP) to that of DOC-salt WT mice, an additional group of DOC-salt alpha-CGRP KO mice was given 0.025% hydralazine to drink. The DOC-salt protocol increased the final MAP in alpha-CGRP KO mice to 155 +/- 6 mmHg and in WT mice to 140 +/- 5 mmHg. The MAP of the hydralazine-treated DOC-salt alpha-CGRP KO mice was 139 +/- 6 mmHg. Urinary excretion of microalbumin and isoprostane, a marker for oxidative stress, was increased, and creatinine clearance was decreased in DOC-salt alpha-CGRP KO compared with DOC-salt WT mice. Equalization of the MAP in DOC-salt alpha-CGRP KO to that of DOC-salt WT mice did not significantly improve these parameters. Renal macrophage infiltration; desmin, a marker of podocyte damage; and the inflammatory cytokines TNF-alpha and IFN-gamma and the chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) were increased in DOC-salt alpha-CGRP KO mice and were not reduced by hydralazine treatment. However, BP equalization did improve the renal histopathological damage, as determined by light microscopy. Therefore, in DOC-salt hypertension in mice, the mechanism(s) of the renal protective effects of alpha-CGRP are both BP independent and BP dependent. |
