Angiotensin II type 1 receptor blocker reduces monocyte adhesion to endothelial cells in spontaneously hypertensive rats

Endocr J. 2007 Aug;54(4):605-12. doi: 10.1507/endocrj.k07-004. Epub 2007 Jul 20.

Abstract

Monocyte adhesion to arterial endothelial cells is the initial step in atherosclerosis. Whereas angiotensin II is known to elicit leukocyte adhesion, it is not clear whether blockade of the angiotensin II receptor signaling reduces monocyte adhesion to endothelial cells beyond its antihypertensive action. This study compared the effect of two different antihypertensive drugs on monocyte adhesion to thoracic aorta endothelium in spontaneously hypertensive rats (SHR): the angiotensin II receptor blocker, valsartan (20 mg . kg(-1) . day(-1)) and the vasodilator, hydralazine (0.75 mg . kg(-1) . day(-1)). The effects were quantitated in vivo using an enface method that optimizes the observation of endothelial surfaces after immunohistochemical staining for CD68. Both agents significantly and comparably reduced blood pressure over 4-week treatment course. Both valsartan and hydralazine profoundly reduced monocyte adhesion compared with nontreated controls, with valsartan having a modestly more reductive effect. Both agents also reduced the intima and medial thickening with valsartan reducing the mean thickness modestly more than hydralazine. Our data confirms that the reduction of blood pressure is effective method to reduce monocyte adhesion. Also, our date demonstrates that valsartan has a modest beneficial effect on monocyte adhesion to endothelial cells and arterial intima-medial vessel thickening beyond its action as an antihypertensive agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Aorta / pathology
  • Atherosclerosis / drug therapy
  • Atherosclerosis / immunology
  • Atherosclerosis / pathology
  • Blood Pressure / drug effects
  • Cell Adhesion / drug effects*
  • Cell Adhesion / immunology
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / urine
  • Endothelial Cells / cytology*
  • Hydralazine / pharmacology
  • Hypertension / drug therapy*
  • Hypertension / immunology
  • Hypertension / pathology
  • Male
  • Monocytes / cytology*
  • Rats
  • Rats, Inbred SHR
  • Tetrazoles / pharmacology*
  • Tunica Intima / pathology
  • Tunica Media / pathology
  • Valine / analogs & derivatives*
  • Valine / pharmacology
  • Valsartan

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Tetrazoles
  • Hydralazine
  • Valsartan
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Valine