title: Renal protective effects of α-calcitonin gene-related peptide in deoxycorticosterone-salt hypertension.
abstract: Deoxycorticosterone salt (DOC-salt) hypertension-induced renal damage is enhanced in α-calcitonin gene-related peptide (α-CGRP) knockout (KO) compared with wild-type (WT) mice. However, since the α-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 α-CGRP enhances hypertension-induced renal damage, DOC-salt hypertension was induced in telemetry probe implanted α-CGRP KO and WT mice. To equalize the blood pressure (BP) to that of DOC-salt WT mice, an additional group of DOC-salt α-CGRP KO mice was given 0.025% hydralazine to drink. The DOC-salt protocol increased the final MAP in α-CGRP KO mice to 155 ± 6 mmHg and in WT mice to 140 ± 5 mmHg. The MAP of the hydralazine-treated DOC-salt α-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 α-CGRP KO compared with DOC-salt WT mice. Equalization of the MAP in DOC-salt α-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-α and IFN-γ and the chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) were increased in DOC-salt α-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 α-CGRP are both BP independent and BP dependent.
authors: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors: Jianping
authors: J
authors: Li
authors: Kevin A
authors: KA
authors: Carnevale
authors: Donald J
authors: DJ
authors: Dipette
authors: Scott C
authors: SC
authors: Supowit
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003893:Desmin / Q000096:biosynthesis; D003900:Desoxycorticosterone; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout
chemical_list: D018925:Chemokines; D016207:Cytokines; D003893:Desmin; D006830:Hydralazine; D003900:Desoxycorticosterone; D015740:Calcitonin Gene-Related Peptide