Angiotensin II, mechanotransduction, and pulsatile arterial hemodynamics in hypertension

Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1567-75. doi: 10.1152/ajpheart.00622.2009. Epub 2009 Sep 4.

Abstract

The aortic blood pressure curve involves two components: a steady component, the mean arterial pressure (MAP), which is dependent on cardiac output and vascular resistance, and a pulsatile component pulse pressure (PP), which is dependent on arterial stiffness and pulse wave reflections. The transduction mechanisms of MAP and PP differ markedly, involving focal adhesion kinase for MAP and oxygen free radicals for PP. Angiotensin II (ANG II) and its blockade are associated with changed vascular resistance and MAP; however, their effects on PP (peripheral and mostly central PP) have been inadequately investigated. In hypertensive rats, when compared with their normotensive controls, ANG II blockade normalizes central PP (<50 mmHg) but not MAP when the same drug dosage is used for each. In hypertensive patients, ANG II blockade reduces arterial stiffness and pulse wave reflections, but with the same reduction in MAP, there is a greater reduction in central than peripheral PP, thereby increasing carotid-brachial PP amplification. With long-term ANG II blockade, the hypertensive arteriolar hypertrophy observed at baseline is corrected in association with reduced arteriolar reflection coefficients, reduced carotid arterial attachments linking alpha(5)-integrin to its ligand fibronectin, and decreased circulating C-reactive protein. When given a normal salt diet, each of these factors contributes separately in reducing arterial stiffness and wave reflections. These responses disappear with a high-salt diet, a condition that usually involves the activation of the local vascular renin-angiotensin-aldosterone system and can be prevented by its selective blockade. Thus ANG II inhibition seems to contribute independently in reducing central PP and aortic stiffness.

Publication types

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

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / physiopathology
  • Blood Pressure / drug effects*
  • Cardiac Output / drug effects
  • Disease Models, Animal
  • Elasticity
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Mechanotransduction, Cellular / drug effects*
  • Pulsatile Flow / drug effects*
  • Renin-Angiotensin System / drug effects
  • Sodium Chloride, Dietary / metabolism
  • Time Factors
  • Treatment Outcome
  • Vascular Resistance / drug effects

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Sodium Chloride, Dietary
  • Angiotensin II