Published Online
on May 31, 2005

A more recent version of this article appeared on July 1, 2005

This Article Full Text (PDF) Data Supplement All Versions of this Article: 46/1/51    most recent 01.HYP.0000168926.44648.edv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bowers, M. C. Articles by Supowit, S. C. Search for Related Content PubMed PubMed Citation Articles by Bowers, M. C. Articles by Supowit, S. C. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Hazardous Substances DB SODIUM CHLORIDE Related Collections Cardio-renal physiology/pathophysiology Animal models of human disease Other hypertension

Submitted on February 14, 2005
Revised on February 28, 2005

Role of Calcitonin Gene-Related Peptide in Hypertension-Induced Renal Damage

Mark C. Bowers; Khurshed A. Katki; Arundhati Rao; Michael Koehler; Parag Patel; Alvin Spiekerman; Donald J. DiPette; and Scott C. Supowit^*

From Texas A&M University System Health Science Center, College of Medicine and Scott & White Health System, Department of Medicine (M.C.B., K.A.K., M.K., D.J.D., S.C.S.), Temple, Tex; Scott & White Health System (A.R., P.P., A.S.), Department of Pathology, Temple, Tex.

^* To whom correspondence should be addressed. E-mail: ssupowit{at}swmail.sw.org.

Abstract--Calcitonin gene-related peptide, a potent vasodilator neuropeptide, is localized in perivascular sensory nerves. We have reported that -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 -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 -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 -calcitonin gene-related peptide, appear to be renoprotective against hypertension-induced damage.

Key words: calcitonin gene-related peptide • hypertension • kidney

This article has been cited by other articles:

				T. Ditting, G. Tiegs, K. Rodionova, P. W. Reeh, W. Neuhuber, W. Freisinger, and R. Veelken Do distinct populations of dorsal root ganglion neurons account for the sensory peptidergic innervation of the kidney? Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1427 - F1434. [Abstract] [Full Text] [PDF]

				R. Huang, A. Karve, I. Shah, M. C. Bowers, D. J. DiPette, S. C. Supowit, and G. S. Abela Deletion of the mouse {alpha}-calcitonin gene-related peptide gene increases the vulnerability of the heart to ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1291 - H1297. [Abstract] [Full Text] [PDF]

				Y. Wang, A. F. Chen, and D. H. Wang Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3136 - H3143. [Abstract] [Full Text] [PDF]

				K. Tsuda, M. C. Bowers, K. A. Katki, A. Rao, M. Koehler, P. Patel, A. Spiekerman, D. J. DiPette, and S. C. Supowit Calcitonin Gene-Related Peptide and Sympathetic Nervous System in Hypertension-Induced Renal Damage Hypertension, December 1, 2005; 46(6): e23 - e24. [Full Text] [PDF]