Ventricular adrenomedullin levels correlate with the extent of cardiac hypertrophy in rats

Hypertension. 1999 May;33(5):1146-52. doi: 10.1161/01.hyp.33.5.1146.

Abstract

We investigated the pathophysiological significance of adrenomedullin (AM) in the development of left ventricular hypertrophy (LVH). LVH was produced by aortic banding (AB) in rats. The left ventricular weight/body weight (LV/BW) ratio, ventricular AM peptide and mRNA levels, and hemodynamics were measured at 1, 3, 7, and 21 days after the operation. Both LV/BW ratio and ventricular AM levels showed a significant increase from 1 day after the operation in the AB rats versus the sham-operated rats. Both increased in a time-dependent manner. The ventricular AM levels correlated with the LV/BW ratio (r=0.76, P<0.01). The AM mRNA levels were highly expressed at 1 day after the operation in the AB rats but showed no difference from 3 to 21 days after the operation between the AB and sham groups. The plasma AM levels showed a peak at 1 day after the operation in both groups. Then, we treated AB rats with an angiotensin-converting enzyme inhibitor (quinapril) in 2 doses (1 and 10 mg. kg-1. d-1) for 21 days. The quinapril treatment attenuated similarly both the LV/BW ratio and the ventricular AM levels. We also assessed the effects of AM and hydralazine administration for 7 days on the LV/BW ratio and hemodynamics of AB rats. Both AM and hydralazine administration reduced the blood pressure by approximately 10% compared with the nontreated AB rats, but a reduction of the LV/BW ratio was observed only in the AM-treated group (P<0.05). These results suggest that ventricular AM levels are elevated by chronic pressure overload in a time-dependent manner concomitant with the extent of LVH and that AM may play a pathophysiological role in the development of LVH in chronic pressure overload.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin
  • Aldosterone / blood
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology
  • Body Weight
  • Calcitonin Gene-Related Peptide / analysis
  • Calcitonin Gene-Related Peptide / genetics
  • Calcitonin Gene-Related Peptide / physiology*
  • Data Interpretation, Statistical
  • Gene Expression
  • Heart Ventricles / chemistry
  • Hemodynamics
  • Hydralazine / administration & dosage
  • Hydralazine / pharmacology
  • Hypertrophy, Left Ventricular / physiopathology*
  • Immunohistochemistry
  • Isoquinolines / administration & dosage
  • Isoquinolines / pharmacology
  • Kidney / drug effects
  • Male
  • Organ Size
  • Peptides / analysis
  • Peptides / genetics
  • Peptides / physiology*
  • Prodrugs
  • Quinapril
  • RNA, Messenger / analysis
  • Radioimmunoassay
  • Rats
  • Rats, Wistar
  • Renin / blood
  • Tetrahydroisoquinolines*
  • Time Factors
  • Ventricular Pressure

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Isoquinolines
  • Peptides
  • Prodrugs
  • RNA, Messenger
  • Tetrahydroisoquinolines
  • Adrenomedullin
  • Hydralazine
  • Aldosterone
  • Renin
  • Calcitonin Gene-Related Peptide
  • Quinapril