In vitro and in vivo vascular actions of basic fibroblast growth factor (bFGF) in normotensive and spontaneously hypertensive rats.
In the cardiovascular system, basic fibroblast growth factor (bFGF) is an important modulator of blood vessel growth and blood pressure and, as such, could contribute to the structural and functional changes that contribute to hypertension. This study evaluated in vitro and in vivo vascular actions of bFGF in normotensive and hypertensive rats. Basic FGF increased the expression of the messenger RNA (mRNA) encoding for the immediate early gene, egr-1, in cultured vascular smooth muscle cells (VSM) isolated from normotensive Wistar-Kyoto (WKY). Sprague-Dawley (SD), and spontaneously hypertensive rats (SHRs). Maximal increases (stimulated/control) in egr-1 mRNA were greater in SHR than in WKY and SD rat VSM (14.57 +/- 1.94 vs. 5.75 +/- 0.35 and 3.84 +/- 0.70). Basic FGF (30 ng/ml) stimulated the growth of WKY (43 +/- 8.4% of growth in 10% serum) and SD (34.6 +/- 6.5%) rat and SHR (75.8 +/- 8.8%) VSM but was most efficacious at stimulating SHR VSM. Radioligand-binding assays indicated no differences in the affinity or number of high-affinity receptors but that the binding of bFGF to low-affinity receptors was slightly but significantly greater in SHR VSM. In vivo, bFGF vasodilated cremaster arterioles in normotensive but not in hypertensive rats. These data suggest that hypertensive animals are more responsive to the growth-stimulatory actions but are less responsive to the vasodilatory actions of bFGF. This altered bFGF function could contribute to the development or maintenance or both of hypertension.
Damon
D H
DH
Department of Pharmacology, University of Texas Health Science Center at San Antonio, USA.
Lange
D L
DL
Hattler
B G
BG
D000818:Animals; D018929:Cell Culture Techniques; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology*; D017874:Immediate-Early Proteins; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2