Load versus humoral activation in the genesis of early hypertensive heart disease

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

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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 (τ) 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. τ 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.

Original languageEnglish (US)
Pages (from-to)215-220
Number of pages6
JournalCirculation
Volume104
Issue number2
DOIs
StatePublished - Jul 10 2001

Keywords

  • Angiotensin
  • Endothelin
  • Hemodynamics
  • Hypertension
  • Hypertrophy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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