RGD Reference Report - Role of calcitonin gene-related peptide in hypertension-induced renal damage. - Rat Genome Database

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Role of calcitonin gene-related peptide in hypertension-induced renal damage.

Authors: Bowers, MC  Katki, KA  Rao, A  Koehler, M  Patel, P  Spiekerman, A  DiPette, DJ  Supowit, SC 
Citation: Bowers MC, etal., Hypertension. 2005 Jul;46(1):51-7. Epub 2005 May 31.
RGD ID: 7204486
Pubmed: PMID:15928032   (View Abstract at PubMed)
DOI: DOI:10.1161/01.HYP.0000168926.44648.ed   (Journal Full-text)

Calcitonin gene-related peptide, a potent vasodilator neuropeptide, is localized in perivascular sensory nerves. We have reported that alpha-calcitonin gene-related peptide knockout mice have elevated baseline blood pressure and enhanced hypertension-induced renal damage compared with wild-type controls. Thus, the aim of this study was to determine the mechanism and functional significance of this increased hypertension-induced renal damage. We previously demonstrated by telemetric recording that the deoxycorticosterone-salt protocol produces a 35% increase in mean arterial pressure in both alpha-calcitonin gene-related peptide knockout and wild-type mice. Both strains of mice were studied at 0, 14, and 21 days after deoxycorticosterone-salt hypertension. Renal sections from hypertensive wild-type mice showed no pathological changes at any time point studied. However, on days 14 and 21, hypertensive knockout mice displayed progressive increases in glomerular proliferation, crescent formation, and tubular protein casts, as well as the inflammatory markers intercellular adhesion molecule-1, vascular adhesion molecule-1, and monocyte chemoattractant protein-1. There was a significant increase in 24-hour urinary isoprostane, a marker of oxidative stress-induced lipid peroxidation, levels at days 14 and 21 in the hypertensive knockout compared with hypertensive wild-type mice. Urinary microalbumin was significantly higher (2-fold) at day 21 and creatinine clearance was significantly decreased 4-fold in the hypertensive knockout compared with hypertensive wild-type mice. Therefore, in the absence of alpha-calcitonin gene-related peptide, deoxycorticosterone-salt hypertension induces enhanced oxidative stress, inflammation, and renal histopathologic damage, resulting in reduced renal function. Thus, sensory nerves, via alpha-calcitonin gene-related peptide, appear to be renoprotective against hypertension-induced damage.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Progressive Renal Failure with Hypertension  ISOCalca (Mus musculus)7204486; 7204486 RGD 
Progressive Renal Failure with Hypertension  IMP 7204486 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Calca  (calcitonin-related polypeptide alpha)

Genes (Mus musculus)
Calca  (calcitonin/calcitonin-related polypeptide, alpha)

Genes (Homo sapiens)
CALCA  (calcitonin related polypeptide alpha)

Additional Information