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A selective somatostatin type-2 receptor agonist inhibits neointimal thickening and enhances endothelial cell growth and morphology following aortic balloon injury in the rabbit

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Abstract

Somatostatin analogs have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation and attenuate neointimal thickening following experimental balloon catheter injury. In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thickening and endothelial cell regrowth 2 weeks following balloon catheterization of male New Zealand White rabbits were determined. Rabbits treated 2 days prior to and 2 weeks after catheter injury with 10 μg/kg/day PRL-2486 (PRL-tx) had decreased I/M ratios (intimal area/medial area × 100; p < 0.05) but had no effect at lower (5 μg/kg/day) or higher (20 μg/kg/day) doses. PRL-tx had significantly decreased VSMC proliferation compared to untreated animals. PRL-tx increased endothelial regrowth by over 2-fold (p < 0.002) and improved endothelial cell morphology. Endothelial-dependent relaxation responses to acetylcholine were attenuated by catheter injury, and were not improved with PRL-tx. These data suggest that the PRL-2486-mediated inhibition of neointimal thickening exhibits a bell-shaped dose-response curve. This inhibition may be due in part to decreased VSMC proliferation, which may be a function of enhanced endothelial regrowth, but not the return of endothelium-dependent vascular function.

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Authors and Affiliations

  1. Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, 70112, USA

    Natali K. Schiller, Alvin M. Timothy & Harmeet S. Aurora

  2. Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA, 70112, USA

    I-Li Chen

  3. Department of Medicine, Tulane University School of Medicine, New Orleans, LA, 70112, USA

    David H. Coy & William A. Murphy

  4. Department of Surgery, Tulane University School of Medicine, New Orleans, LA, 70112, USA

    Donald L. Akers

  5. Departments of Pharmacology and Medicine, Tulane University School of Medicine, New Orleans, LA, 70112, USA

    Vivian A. Fonseca

  6. Departments of Pharmacology and Surgery, Tulane University School of Medicine, New Orleans, LA, 70112, USA

    Philip J. Kadowitz & Dennis B. McNamara

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  1. Natali K. Schiller
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  2. Alvin M. Timothy
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  4. I-Li Chen
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  9. Philip J. Kadowitz
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  10. Dennis B. McNamara
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Schiller, N.K., Timothy, A.M., Aurora, H.S. et al. A selective somatostatin type-2 receptor agonist inhibits neointimal thickening and enhances endothelial cell growth and morphology following aortic balloon injury in the rabbit. Mol Cell Biochem 240, 31–37 (2002). https://doi.org/10.1023/A:1020679809056

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