[Cellular adhesion to elements of the extracellular matrix in the hypertensive rat modulates the effect of angiotensin II]

Arch Mal Coeur Vaiss. 1999 Aug;92(8):1053-7.
[Article in French]

Abstract

This study was to assess the role of different components of the extracellular matrix (ECM) on the mobilization of Cai++ induced by angiotensin II in vascular smooth muscle cells (VSMC) from hypertensive (SHR) and normotensive (WKY) rats. The effect of AII (10-6 M) on Cai++ release was studied in VSMC isolated from the aorta of 5-week-old WKY and SHR using fluorescent imaging microscopy (fura-2). Cai++ mobilization was characterized by amplitude, slope of Cai++ increase and total amount of Cai++. Cells were cultured on glass coverslips (control) or coated with either collagen I, collagen IV, vitronectin, fibronectin and extracellular matrix (ECM) and studied at confluence between passage 3 and 9. A significant increase of Cai++ released by AII has been observed with cells from WKY cultured on collagen I (meam +/- SEM, amplitude: 192 +/- 12% of control values, slope: 194 +/- 13%, total amount Cai++: 173 +/- 12%, n = 270, p < or = 0.0001 for each, unpaired t-test). Conversely, response with SHR was not significatively modified. Cai++ mobilization was not significatively modified after culture of VSMC from SHR and WKY on collagen IV. A significative decrease of the slope (WKY: 66 +/- 6%, p < or = 0.0001; SHR: 83 +/- 5%, p < or = 0.03) and of the amount of Cai++ (WKY: 74 +/- 7%, p < or = 0.01; SHR: 74 +/- 5%, p < or = 0.01) has been observed after culture of VSMC from the 2 strains on vitronectin. A decrease in amplitude (53 +/- 3%, p < or = 0.0001), slope (38 +/- 4%, p < or = 0.0001) and Cai++ release (69 +/- 5%, p < or = 0.004, n = 106) has been observed in VSMC from SHR seeded on fibronectin. Conversely, in VSMC from WKY, Cai++ mobilisation has not been modified compared with control cells. Culture of VSMC from SHR on ECM induced a significative decrease of amplitude (49 +/- 2%), slope (54 +/- 4%) and Cai++ release (53 +/- 3%, p < or = 0.0001 for each, n = 122), while in WKY, ECM induced a significative stimulation of these parameters (amplitude: 157 +/- 11%, slope: 149 +/- 13% and Cai++ release: 130 +/- 9%, p < or = 0.0001 for each, n = 247). These results show that the Cai++ mobilization induced by AII is modified by the adhesion of cells to different ECM components. This suggests a modulation of the A II-associated signalling events via the focal adhesion points. Furthermore, a difference in this modulation is observed between SHR and WKY when cells are seeded on collagen I, fibronectin or ECM. These modulations of Cai++ mobilization could play a role in the regulation of growth and differentiation of cells during the development of hypertension.

Publication types

  • English Abstract

MeSH terms

  • Angiotensin II / therapeutic use*
  • Animals
  • Calcium / metabolism
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Collagen / pharmacology
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Extracellular Matrix / physiology*
  • Fibronectins / pharmacology
  • Hypertension / drug therapy*
  • Hypertension / pathology
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / pathology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Vasoconstrictor Agents / therapeutic use*
  • Vitronectin / pharmacology

Substances

  • Fibronectins
  • Vasoconstrictor Agents
  • Vitronectin
  • Angiotensin II
  • Collagen
  • Calcium