Hypotensive activity of fibroblast growth factor.
Acidic and basic fibroblast growth factors (FGFs) are members of a family of proteins that are broad-spectrum mitogens, have diverse hormone-like activities, and function in tumorigenesis. FGF's ability to raise the concentration of intracellular calcium ion suggests that FGF could induce the synthesis of endothelium-derived relaxing factor (EDRF) and consequently vasodilation. Systemic administration of FGF decreased arterial blood pressure. This effect was mediated by EDRF and by adenosine triphosphate-sensitive potassium ion channels. The hypotensive effect of FGF was segregated from its mitogenic activity by protein engineering. These results extend the range of FGF autocrine activities and potential therapeutic applications, emphasize the role of endothelium as an arterial blood pressure--regulating organ, and provide insight on the structural basis of FGF functions.
Cuevas
P
P
Hospital Universitario Ramón y Cajal, Carretera de Colmenar, Madrid, Spain.
Carceller
F
F
Ortega
S
S
Zazo
M
M
Nieto
I
I
Giménez-Gallego
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D013997:Time Factors
D015221:Potassium Channels; D009569:Nitric Oxide; D005346:Fibroblast Growth Factors; D005905:Glyburide