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(Hypertension. 2005;45:109.)
© 2005 American Heart Association, Inc.

Scientific Contributions

Calcitonin Gene-Related Peptide Protects Against Hypertension-Induced Heart and Kidney Damage

Scott C. Supowit; Arundhati Rao; Mark C. Bowers; Huawei Zhao; Gregory Fink; Barbara Steficek; Parag Patel; Khurshed A. Katki; Donald J. DiPette

From the Texas A&M University System Health Science Center (S.C.S., M.C.B., K.A.K., D.J.D.), College of Medicine and Scott & White Health System, Department of Medicine, Temple, Tex; the Department of Pathology (A.R., P.P.), Scott & White Health System, Temple, Tex; the Department of Pharmacology and Toxicology (H.Z., G.F.), and Diagnostic Center for Population and Animal Health (B.S.), Michigan State University, East Lansing, Mich.

Correspondence to Scott C. Supowit PhD, Texas A&M University Medical Research Building, 702 SW H.K. Dodgen Loop, Temple, TX 76504. E-mail ssupowit{at}swmail.sw.org

Calcitonin gene-related peptide is a potent vasodilator neuropeptide that is localized in perivascular sensory nerves. To determine whether -calcitonin gene-related peptide possesses protective activity against hypertension-induced end organ damage, hypertension was induced in -calcitonin gene-related/calcitonin peptide knockout and wild-type mice by uninephrectomy, deoxycorticosteroid administration, and 0.9% saline drinking water. These mice were instrumented previously for long-term telemetric blood pressure recording. Control groups were sham-operated and given tap water. Mean arterial pressures were determined, and 3 weeks after initiation of each protocol, tissues were taken for histopathologic studies. The deoxycorticosteroid-salt protocol produced a significant 35% mean arterial pressure increase in both mouse strains. No pathological changes were observed in sections of aortas and femoral arteries from any of the groups studied. Likewise, heart and kidney sections from the hypertensive wild-type mice showed no pathological changes compared with their normotensive counterparts. In contrast, marked vasculitis was seen in the heart sections from the deoxycorticosteroid-salt–treated -calcitonin gene-related peptide knockout mice with thickening and inflammation of the vessel walls. In addition, myocarditis and focal epicarditis with areas of myocardial necrosis were present. Kidneys of these mice exhibited prominent glomerular changes including congestion of the capillary loops, focal mesangial and crescent proliferation, and focal histocytic infiltration. Urinary microalbumin was significantly higher in the hypertensive -calcitonin gene-related peptide knockout compared with hypertensive wild-type mice. These data suggest that deletion of the -calcitonin gene-related peptide gene makes the heart and kidneys more vulnerable to hypertension-induced end organ damage.

Key Words: hypertension, experimental • mice • calcitonin gene-related peptide • blood pressure

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