Correction of hypertension by normalization of endothelial levels of fibroblast growth factor and nitric oxide synthase in spontaneously hypertensive rats.
Acidic and basic fibroblast growth factors (FGFs) share a wide range of diverse biological activities. To date, low levels of FGF have not been correlated with a pathophysiologic state. We report that blood vessels of spontaneously hypertensive rats are shown to be associated with a marked decrement in endothelial basic FGF content. This decrement correlates both with hypertension and with a decrease in the endothelial content of nitric oxide synthase. Restoration of FGF to physiological levels in the vascular wall, either by systemic administration or by in vivo gene transfer, significantly augmented the number of endothelial cells with positive immunostaining for nitric oxide synthase, corrected hypertension, and ameliorated endothelial-dependent responses to vasoconstrictors. These results suggest an important role for FGFs in blood pressure homeostasis and open new avenues for the understanding of the etiology and treatment of hypertension.
Cuevas
P
P
Hospital Universitario Ramón y Cajal, Carretera de Colmenar, Madrid, Spain.
García-Calvo
M
M
Carceller
F
F
Reimers
D
D
Zazo
M
M
Cuevas
B
B
Muñoz-Willery
I
I
Martínez-Coso
V
V
Lamas
S
S
Giménez-Gallego
G
G
D000818:Animals; D001013:Aorta, Thoracic; D001794:Blood Pressure / Q000187:drug effects*; D010450:Endopeptidases; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage / Q000096:biosynthesis* / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015316:Genetic Therapy; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000096:biosynthesis; D012038:Regeneration; D014162:Transfection
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D010450:Endopeptidases