title: Effect of interleukin 8 and ICAM-1 on calcium-dependent outflow of K+ in erythrocytes from subjects with essential hypertension.
abstract: BACKGROUND
  The pathogenic mechanisms underlying the increase in peripheral resistance and the contraction of smooth muscular fibre cells in essential hypertension are not yet clearly understood. However, it is now known that immune system activation plays a role in the pathogenesis of some forms of arterial hypertension, and recent data show that the Ca2+ influx in some cells (i.e. red blood cells, leukocytes, platelets, smooth muscular fibre cells) is increased in subjects with essential hypertension, thus revealing a possible alteration in cellular membrane. The end-points of this study were therefore to ascertain whether red blood cells used as a cellular membrane model have a greater Ca2+ dependent K+ flow (Gardos effect) in hypertensive patients than in normotensive controls, to point out a different regulation of ionic channels, and whether IL-8 and the adhesion molecule ICAM-1 influence the membranous outflow.
  
  
  METHODS
  The study was conducted on 87 Caucasian subjects. Of these, 50 (25 men, 25 women; mean age 43 +/- 3 years, mean body mass index (BMI) 27 +/- 0.5 and 22.3 +/- 0.3 kg/m(2), respectively) had mild-to-moderate hypertension (mean arterial blood pressure 120 +/- 8 mmHg ). The other 37 (18 men, 19 women; mean age 39 +/- 3 years; BMI 23.8 +/- 0.5 kg/m(2) and 22.8 +/- 0.5 kg/m(2), respectively were normotensive healthy volunteers (mean arterial blood pressure 89 +/- 2 mmHg). All the patients and subjects were untreated for at least 4 weeks before blood sampling.
  
  
  RESULTS
  Ca2+-dependent K+ outflow was found to be greater in samples from patients with essential hypertension than in those from normotensive controls. lL-8 and ICAM-1 significantly enhanced the Ca2+-dependent K+ outflow in red blood cells from hypertensive subjects but had an inhibitory effect on cells from controls. In the experimental model, the presence of TMB-8, a membrane calcium antagonist, significantly reduced the Ca2+-dependent K+ efflux.
  
  
  CONCLUSIONS
  Vasoconstriction in subjects with essential hypertension may therefore depend on a different regulation of ionic flow that probably supports an increased Ca2+ inflow in smooth muscle fibre cells. Under certain pathological conditions, some immune system components (i.e. interleukins, adhesion molecules) may directly enhance membrane permeability to Ca2+, thus inducing vasoconstriction in the smooth muscle cells.
authors.affiliation: Department of Internal Medicine, University of Messina, Via Salita Villa Contino 30. 98100 Messina, Italy. Buemim@unime.it
authors.forename: M
authors.initials: M
authors.lastname: Buemi
authors.forename: D
authors.initials: D
authors.lastname: Marino
authors.forename: F
authors.initials: F
authors.lastname: Floccari
authors.forename: A
authors.initials: A
authors.lastname: Ruello
authors.forename: L
authors.initials: L
authors.lastname: Nostro
authors.forename: C
authors.initials: C
authors.lastname: Aloisi
authors.forename: M T
authors.initials: MT
authors.lastname: Marino
authors.forename: G
authors.initials: G
authors.lastname: Di Pasquale
authors.forename: F
authors.initials: F
authors.lastname: Corica
authors.forename: N
authors.initials: N
authors.lastname: Frisina
mesh_terms: D000328:Adult; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000502:physiology*; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D016209:Interleukin-8 / Q000502:physiology*; D008297:Male; D011188:Potassium / Q000097:blood*; D015221:Potassium Channels / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D016209:Interleukin-8; D015221:Potassium Channels; D018799:Intercellular Adhesion Molecule-1; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011188:Potassium; D002118:Calcium