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Viral‐Mediated Gene Delivery Of Constitutively Activated GΑS Alters Vasoreactivity
Author(s) -
Schutzer William E,
Watts Val J,
Chapman Justin,
Cumbay Medhane G,
Neve Kim A,
Neve Rachael L,
Mader Scott L
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03210.x
Subject(s) - phenylephrine , vascular smooth muscle , endocrinology , medicine , herpes simplex virus , biology , forskolin , signal transduction , alpha (finance) , receptor , microbiology and biotechnology , stimulation , virus , immunology , nursing , smooth muscle , patient satisfaction , blood pressure , construct validity
SUMMARY 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 G α s (G α s‐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 G α s 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–G α s‐Q227L had reduced phenylephrine‐induced contraction and enhanced isoproterenol‐stimulated vasorelaxation. Infection of cultured VSMC with HSV–G α s‐Q227L increased both basal‐ and isoproterenol‐stimulated cAMP accumulation, whereas forskolin‐stimulated cAMP production was unchanged. 4. These results implicate G α s 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.