Role of contractile agonists in growth regulation of vascular smooth muscle cells.
There is now clear evidence demonstrating that contractile agonists such as angiotensin II and arginine vasopressin are potent hypertrophic agents for cultured vascular smooth muscle cells. Furthermore, there is circumstantial evidence supporting a role for these factors in mediation of smooth muscle cell hypertrophy in hypertensive animal models as well as in maintenance of contractile mass in normotensive animals. At least part of the hypertrophic effect of angiotensin II and arginine vasopressin appears to involve a generalized increase in protein synthesis since the synthesis of most if not all proteins is increased to some extent. However, in addition, these agonists also stimulate large selective increases in the synthesis and content of a number of cytoskeletal and smooth muscle cell specific contractile proteins, including smooth muscle alpha-actin. The latter result is quite exciting since it suggests that contractile agonists may play an important role in regulation of developmental growth and differentiation of vascular smooth muscle as well as in modulating the contractile mass of smooth muscle tissues in accordance with functional demands. Observations that agonists increase expression of smooth muscle alpha-actin mRNA show that hypertrophy is not regulated solely at the translational level, although it remains to be determined whether changes are mediated transcriptionally and/or post-transcriptionally. In any event, further examination of the mechanisms whereby contractile agonists alter expression of these proteins should provide important insight regarding how these factors act as hypertrophic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Owens
G K
GK
Department of Physiology, University of Virginia School of Medicine, Charlottesville 22908.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000473:pathology; D006984:Hypertrophy; D008934:Mitogens / Q000494:pharmacology; D024510:Muscle Development; D009124:Muscle Proteins / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D008934:Mitogens; D009124:Muscle Proteins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin