The inflammatory aspect of the microcirculation in hypertension: Oxidative stress, leukocytes/endothelial interaction, apoptosis

Makoto Suematsu, Hidekazu Suzuki, Frank A. Delano, Geert W. Schmid-Schönbein

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Evidence is increasing in hypertensive models for an inflammatory reaction in the microcirculation with abnormal leukocyte counts and adhesion to the endothelium, enhanced arteriolar tone, and microvascular and tissue apoptosis. The spontaneous form of hypertension (SHR) is accompanied by a glucocorticoid-dependent increase in circulating leukocyte count with elevated levels of activation and at the same time depressed leukocyte-endothelial interaction and endothelial P-selectin function. The SHR exhibits immune suppression with lymphocyte apoptosis in the thymus. Generation of reactive oxygen species (ROS) in and around microvascular endothelial cells may regulate signal transduction pathways responsible for controlling gene expression and protein modification and thereby cause an elevation of vascular tone and, in excess, may form an injury mechanism for cells and tissue. A series of enzyme systems such as xanthine oxidase, reduced nicotinamide adenine dinucleotide phosphate/reduced nicotinamide adenine dinucleotide oxidase, and cytochrome P450 monooxygenases in conjunction with suppression of ROS scavengers seem to be involved in the oxidative stress responses in hypertension. The increase in ROS generation contributes to vascular remodeling, apoptosis, and proliferation of vascular smooth muscle, whereas gaseous monoxides such as nitric oxide and carbon monoxide have the ability to modulate elevated vascular tone and proliferative cell responses. Such biological actions of gases not only regulate activation of soluble guanylate cyclase but could also be attributable to inhibition of cytochrome P450 monooxygenases. We examine here the molecular basis of signal transduction by ROS, NO, and CO and functional alterations in their sensor molecules. An inflammatory reaction may underlie the pathogenesis of hypertension and its associated lesion formation and organ dysfunction.

Original languageEnglish
Pages (from-to)259-276
Number of pages18
JournalMicrocirculation
Volume9
Issue number4
DOIs
Publication statusPublished - 2002 Dec 1

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Keywords

  • Carbon monoxide
  • Endothelium
  • Glucocorticoids
  • Hydrogen peroxide
  • Leukocytes
  • Mineralocorticoids
  • Nitric oxide
  • Selectins
  • Soluble guanylate cyclase
  • Superoxide

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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