This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Hart, C. Y.T. Articles by Redfield, M. M. Search for Related Content PubMed PubMed Citation Articles by Hart, C. Y.T. Articles by Redfield, M. M. Related Collections Cardio-renal physiology/pathophysiology Animal models of human disease Heart failure - basic studies Hypertension - basic studies

(Circulation. 2001;104:215.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Load Versus Humoral Activation in the Genesis of Early Hypertensive Heart Disease

Chari Y.T. Hart, MD; Donna M. Meyer; Henry D. Tazelaar, MD; Joseph P. Grande, MD; John C. Burnett Jr, MD; Philippe R. Housmans, MD; Margaret M. Redfield, MD

From the Division of Cardiovascular Diseases and Internal Medicine (C.Y.T.H., D.M.M., J.C.B., M.M.R), Department of Laboratory Medicine and Pathology (H.D.T., J.P.G.), and Department of Anesthesiology (P.R.H.), Mayo Clinic, Rochester, Minn.

Correspondence to Margaret M. Redfield, MD, Division of Cardiovascular Diseases and Internal Medicine, 200 First St Southwest, Rochester, MN 55905. E-mail redfield.margaret{at}mayo.edu

Background—— The role of load versus angiotensin II (Ang II) and endothelin-1 (ET) in the pathogenesis of hypertensive heart disease is controversial. We sought to determine whether alterations in cardiac structure and function due to hypertension (HTN) were dependent on Ang II or ET activation.

Methods and Results—— Bilateral renal wrapping to produce HTN (n=12) or sham surgery (n=6) was performed in adult dogs. Weekly blood pressure, plasma renin activity, Ang II, ET, and catecholamines were measured. Systolic (end-systolic elastance, Ees) and diastolic () function were assessed in sham and HTN dogs at 5 (HTN-5wk) or 12 (HTN-12wk) weeks. Ang II and ET were assayed in the left ventricle (LV) and kidney. Mean arterial pressure was higher in renal wrap dogs at week 1 (*P<0.05 versus controls: 139±4* versus 123±4 mm Hg), week 5 (174±7* versus 124±4 mm Hg), and week 12 (181±12* versus 124±4 mm Hg). LV mass index was increased in HTN-5wk (22%*) and HTN-12wk (39%*). LV fibrosis was increased in HTN-12wk. Ees was preserved in HTN-5wk and HTN-12wk. was increased in HTN-5wk (50±3* ms) and HTN-12wk (62±10* ms) dogs compared with sham (41±2 ms). Plasma Ang II, ET, catecholamines, and plasma renin activity were unchanged during the progressive HTN. Ang II and ET in LV and kidney were not different from controls.

Conclusions—— Systemic HTN induces LV hypertrophy, myocardial fibrosis, and isolated diastolic dysfunction in the absence of local or systemic activation of Ang II or ET. These findings suggest that load is the prevailing stimulus for the structural and functional changes associated with early hypertensive heart disease.

Key Words: hypertension • hypertrophy • hemodynamics • angiotensin • endothelin

This article has been cited by other articles:

				W. A. Jaber, C. Maniu, J. Krysiak, B. P. Shapiro, D. M. Meyer, W. A. Linke, and M. M. Redfield Titin Isoforms, Extracellular Matrix, and Global Chamber Remodeling in Experimental Dilated Cardiomyopathy: Functional Implications and Mechanistic Insight Circ Heart Fail, September 1, 2008; 1(3): 192 - 199. [Abstract] [Full Text] [PDF]

				W. A. Jaber, C. S. P. Lam, D. M. Meyer, and M. M. Redfield Revisiting methods for assessing and comparing left ventricular diastolic stiffness: impact of relaxation, external forces, hypertrophy, and comparators Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2738 - H2746. [Abstract] [Full Text] [PDF]

				B. P. Shapiro, C. S.P. Lam, J. B. Patel, S. F. Mohammed, M. Kruger, D. M. Meyer, W. A. Linke, and M. M. Redfield Acute and Chronic Ventricular-Arterial Coupling in Systole and Diastole: Insights From an Elderly Hypertensive Model Hypertension, September 1, 2007; 50(3): 503 - 511. [Abstract] [Full Text] [PDF]

				V. K. Munagala, C. Y.T. Hart, J. C. Burnett Jr, D. M. Meyer, and M. M. Redfield Ventricular Structure and Function in Aged Dogs With Renal Hypertension: A Model of Experimental Diastolic Heart Failure Circulation, March 8, 2005; 111(9): 1128 - 1135. [Abstract] [Full Text] [PDF]

				R. M. Fagugli, P. Pasini, G. Quintaliani, F. Pasticci, G. Ciao, B. Cicconi, D. Ricciardi, P. V. Santirosi, E. Buoncristiani, F. Timio, et al. Association between extracellular water, left ventricular mass and hypertension in haemodialysis patients Nephrol. Dial. Transplant., November 1, 2003; 18(11): 2332 - 2338. [Abstract] [Full Text] [PDF]

				M. M. Redfield, S. J. Jacobsen, J. C. Burnett Jr, D. W. Mahoney, K. R. Bailey, and R. J. Rodeheffer Burden of Systolic and Diastolic Ventricular Dysfunction in the Community: Appreciating the Scope of the Heart Failure Epidemic JAMA, January 8, 2003; 289(2): 194 - 202. [Abstract] [Full Text] [PDF]

				C. V. Maniu, D. M. Meyer, and M. M. Redfield Hemodynamic and Humoral Effects of Vasopeptidase Inhibition in Canine Hypertension Hypertension, October 1, 2002; 40(4): 528 - 534. [Abstract] [Full Text] [PDF]