Role of chymase-dependent angiotensin II formation in monocrotaline-induced pulmonary hypertensive rats

Pediatr Res. 2006 Jul;60(1):77-82. doi: 10.1203/01.pdr.0000219431.45075.d9. Epub 2006 May 11.

Abstract

Angiotensin II-forming chymase is expressed in the pulmonary arteries of the monocrotaline-induced pulmonary hypertensive rats, but its actual role is unclear. We studied chymase-dependent angiotensin II formation in the pulmonary arteries of the monocrotaline-induced pulmonary hypertensive rats and observed the effects of an angiotensin II receptor blocker on vascular remodeling. Four weeks after the administration of monocrotaline (60 mg/kg, s.q.), echocardiographic, hemodynamic, morphometric and biochemical analyses were performed. Age-matched rats were used as controls. To evaluate the effects of an angiotensin II receptor blocker, 2 wk after beginning of monocrotaline treatment, the rats were given candesartan (10 mg/kg per day) or placebo for 2 wk. In the monocrotaline-induced pulmonary hypertensive rats, the elevated systolic pulmonary arterial pressure and right ventricular hypertrophy were observed. Medial hypertrophy of lung arterioles was also observed. Chymase activity and angiotensin II concentration, but not angiotensin-converting enzyme activity, were significantly increased in the lung. In the angiotensin II receptor blocker-treated group, both systolic pulmonary arterial pressure and right ventricular hypertrophy were significantly reduced, and arteriolar hypertrophy was also prevented. Thus, angiotensin II-forming chymase may play a role in the proliferation of the medial layer in the lung arterioles of monocrotaline-induced pulmonary hypertensive rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / analysis
  • Angiotensin II / metabolism*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin Receptor Antagonists
  • Animals
  • Benzimidazoles / pharmacology
  • Biphenyl Compounds
  • Blood Pressure / drug effects
  • Cell Proliferation
  • Chymases
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / physiopathology
  • Hypertrophy, Right Ventricular / chemically induced
  • Hypertrophy, Right Ventricular / physiopathology
  • Hypertrophy, Right Ventricular / prevention & control
  • Male
  • Monocrotaline
  • Peptidyl-Dipeptidase A / analysis
  • Peptidyl-Dipeptidase A / metabolism
  • Pulmonary Artery / chemistry
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism*
  • Pulmonary Artery / pathology
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Angiotensin / analysis
  • Serine Endopeptidases / analysis
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*
  • Tetrazoles / pharmacology
  • Tunica Media / chemistry
  • Tunica Media / drug effects
  • Tunica Media / metabolism
  • Tunica Media / pathology

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin Receptor Antagonists
  • Benzimidazoles
  • Biphenyl Compounds
  • RNA, Messenger
  • Receptors, Angiotensin
  • Tetrazoles
  • Angiotensin II
  • Monocrotaline
  • Peptidyl-Dipeptidase A
  • Serine Endopeptidases
  • Chymases
  • candesartan