Viral-mediated gene delivery of constitutively activated Gαs alters vasoreactivity

William E. Schutzer, Val J. Watts, Justin Chapman, Medhane G. Cumbay, Kim Neve, Rachael L. Neve, Scott L. Mader

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

1. Decline in β-adrenoceptor (β-AR)-mediated function occurs with increasing age, as well as in multiple disease conditions. The mechanisms responsible for this decline include alterations in β-AR itself, β-AR coupling proteins, such as G-proteins, or other β-AR-linked proteins, such as G-protein receptor kinases and/or phosphatases. 2. The present study examines the physiological effects of in vitro transfer of constitutively activated Gαs (Gαs-Q227L) to both cultured vascular smooth muscle cells (VSMC) and whole aortic tissue of 6-month-old (adult) animals via a replication-deficient Herpes simplex virus (HSV) vector. These studies were conducted to provide a model for future examination of the role of Gαs in the age-related decline in β-AR-mediated vasorelaxation. 3. Gene transfer was confirmed by western blotting for specific proteins. Aortic tissue infected with HSV-Gαs-Q227L had reduced phenylephrine-induced contraction and enhanced isoproterenol-stimulated vasorelaxation. Infection of cultured VSMC with HSV-Gαs-Q227L increased both basal- and isoproterenol-stimulated cAMP accumulation, whereas forskolin-stimulated cAMP production was unchanged. 4. These results implicate Gαs as a target for further investigation in age-related changes in vascular reactivity and support the use of viral-mediated gene transfer as an effective tool to study adrenergic signal transduction and physiology in vascular tissue.

Original languageEnglish (US)
Pages (from-to)9-13
Number of pages5
JournalClinical and Experimental Pharmacology and Physiology
Volume27
Issue number1-2
DOIs
StatePublished - Jan 2000

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Viral Genes
Simplexvirus
Vascular Smooth Muscle
Isoproterenol
Vasodilation
Glycogen-Synthase-D Phosphatase
Smooth Muscle Myocytes
Blood Vessels
Cyclic GMP-Dependent Protein Kinases
Proteins
Phenylephrine
Colforsin
GTP-Binding Proteins
Adrenergic Agents
Adrenergic Receptors
Signal Transduction
Western Blotting
Infection
Genes

Keywords

  • cAMP
  • G-protein
  • Gene transfer
  • Herpes simplex virus
  • Vascular tone
  • Vasorelaxation

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Viral-mediated gene delivery of constitutively activated Gαs alters vasoreactivity. / Schutzer, William E.; Watts, Val J.; Chapman, Justin; Cumbay, Medhane G.; Neve, Kim; Neve, Rachael L.; Mader, Scott L.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 27, No. 1-2, 01.2000, p. 9-13.

Research output: Contribution to journalArticle

Schutzer, William E. ; Watts, Val J. ; Chapman, Justin ; Cumbay, Medhane G. ; Neve, Kim ; Neve, Rachael L. ; Mader, Scott L. / Viral-mediated gene delivery of constitutively activated Gαs alters vasoreactivity. In: Clinical and Experimental Pharmacology and Physiology. 2000 ; Vol. 27, No. 1-2. pp. 9-13.
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