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Vasoactive hormones and cAMP affect pericyte contraction and stress fibresin vitro

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Summary

Pericytes are contractile cells of the microvascular wall that may influence capillary haemodynamics and permeability. We examined the contractile responses of cultured pericytes to selected vasoactive agents and cAMP agonists. Morphological and biochemical changes associated with these responses were also studied. Pericytes seeded onto silicone rubber contracted when stimulated with histamine or serotonin, relaxed in response to the beta-adrenergic agonist isoproterenol and did not respond to epinephrine. Since hormonal-induced relaxation of vascular smooth muscle involves cAMP, we investigated the ability of cAMP, to modulate pericyte contraction. Dibutyryl cAMP and forskolin (an adenylate cyclase activator) both induced pericyte relaxation and elevated intracellular cAMP levels. Isoproterenol increased cAMP levels but epinephrine had no effect. However, when epiniphrine and isoproterenol were co-incubated with the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX), cAMP was increased to levels above those elicited by these agonists alone. Serotonin and histamine in the presence of IBMX did not affect cAMP levels. These results suggest that certain vasoactive agents may relax pericytes by cAMP-dependent processes. We have shown previously that stress fibres are also involved in pericyte contraction. Hence, changes in the staining patterns of stress fibres in response to these selected agonists were studied. Histamine, serotonin and epinephrine had no apparent effect on stress fibre staining. Dibutyryl cAMP, forskolin, and isoproterenol, which relax pericytes and increase cAMP, disassembled fibres. In summary, the results demonstrate that the contractile activity of cultured pericytesin vitro can be regulated by vasoactive agonists and that changes in cAMP and stress fibres may mediate the regulation.

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Abbreviations

cAMP:

cyclic adenosine 3′,5′-monophosphate

dBcAMP:

dibutyryl cyclic adenosine 3′5′-monophosphate

DiL-Ac-LDL:

1,1′-dioctadecyl 1-3,3,3′,3′ tetramethylindo-carbocyanine perchlorate

DME:

Dulbecco's Modified Eagles Medium

FCS:

foetal calf serum

HBSS:

Hanks balanced salt solution

IBMX:

3-isobutyl-1-methylxanthine

PBS:

phosphate buffered saline

R020-1724:

(4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone

TCA:

trichloroacetic acid

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Author notes

  1. Christine Kelley

    Present address: Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA

Authors and Affiliations

  1. Departments of Biology and Surgery, Boston University, Boston, MA, USA

    Christine Kelley, Patricia D'Amore, Herbert B. Hechtman &  David Shepro

  2. Harvard Medical School, Childrens Hospital, 02215, Boston, MA, USA

    Patricia D'Amore

  3. Harvard Medical School, Brigham and Womens Hospital, 02215, Boston, MA, USA

    Herbert B. Hechtman

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  1. Christine Kelley
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  2. Patricia D'Amore
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  3. Herbert B. Hechtman
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  4. David Shepro
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Kelley, C., D'Amore, P., Hechtman, H.B. et al. Vasoactive hormones and cAMP affect pericyte contraction and stress fibresin vitro . J Muscle Res Cell Motil 9, 184–194 (1988). https://doi.org/10.1007/BF01773740

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  • DOI: https://doi.org/10.1007/BF01773740

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