Alpha 1-adrenergic stimulation of platelet-derived growth factor A-chain gene expression in rat aorta.
Sympathetic nerves and catecholamines exert growth-promoting trophic influences on arterial smooth muscle in vivo, but the molecular signals mediating these trophic effects are unknown. We report here that the alpha-adrenergic agonist phenylephrine (PE) produced dose-dependent stimulation of platelet-derived growth factor A-chain (PDGF-A) gene expression in rat thoracic aorta via agonist occupancy of alpha 1-adrenergic receptors. Increases in aortic PDGF-A mRNA levels were rapid (maximal at 6 h, 10-fold) and transient. Among seven different tissues studied, PE evoked significant increases in PDGF-A mRNA levels only in the aorta. When periaortic fatty/connective tissues normally adherent to thoracic aorta were examined separately from the remaining aortic vessel wall (endothelium removed), stimulated PDGF-A gene expression was found only in vessel wall (presumably smooth muscle). The physiological alpha-adrenergic agonist norepinephrine also increased aortic PDGF-A mRNA levels. Angiotensin II or endothelin, despite producing blood pressure increases similar to PE, had little or no effect on PDGF-A mRNA abundance in rat aorta. PE-stimulated PDGF-A gene expression was accompanied by increased expression of other growth-related genes including c-fos, c-myc, and ornithine decarboxylase but not DNA synthesis. These results suggest a mechanism for previously described trophic effects of sympathetic nerves and catecholamines on arterial smooth muscle mass, i.e. regulation of growth-related gene expression via alpha 1-adrenergic receptors.
Majesky
M W
MW
Department of Pathology, University of Washington, Seattle 78195.
Daemen
M J
MJ
Schwartz
S M
SM
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001345:Autoradiography; D001794:Blood Pressure; D015152:Blotting, Northern; D015870:Gene Expression; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D009693:Nucleic Acid Hybridization; D010656:Phenylephrine / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D010982:Platelet-Derived Growth Factor; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D012313:RNA; D009638:Norepinephrine