title: Extracellular signal-regulated kinase pathway is involved in basic fibroblast growth factor effect on angiotensin II-induced Ca(2+) transient in vascular smooth muscle cell from Wistar-Kyoto and spontaneously hypertensive rats.
abstract: We studied the effect of basic fibroblast growth factor (b-FGF) on different Ca(2+) mechanisms elicited by angiotensin II (Ang II) in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Intracellular Ca(2+) (Ca(2+)(i)) variations were studied in cultured vascular smooth muscle cells (VSMCs) isolated from the aorta of 5- to 6-week-old WKY rats and SHR. Ca(2+)(i) was assessed in Fura-2-loaded cells with fluorescent imaging microscopy. Ang II subtype 1 receptor activation by Ang II (1 micromol/L) induced a transient increase in Ca(2+)(i) that was partially attenuated by genistein, a tyrosine kinase inhibitor. Pretreatment of VSMCs with b-FGF for 24 hours markedly stimulated the Ang II-induced Ca(2+)(i) release from the internal stores in WKY rats, whereas it was without effect in SHR. This was not consequent to a change in the affinity of Ang II subtype 1 receptors or an increase in their density. Inhibition of mitogen-activated protein kinase with PD 98059 reduced this stimulatory effect of the cytokine in the WKY rats. On the other hand, b-FGF stimulated the Ang II-induced Ca(2+) influx in both strains. Similar results were observed when Ca(2+) influx was induced with thapsigargin. Genistein and PD 98059 abolished the effect of b-FGF. These results show for the first time that b-FGF regulates Ca(2+) mechanisms induced by Ang II and that this regulation is different in SHR than in normotensive control animals. The extracellular signal-regulated kinase cascade is implicated in this cross-regulation with G protein-signaling pathway at 2 levels and possibly more: 1 at the tyrosine kinases and the other downstream of the extracellular signal-regulated kinase family. These results may prove useful in understanding the interaction between these 2 pathways and their implication in genetic hypertension.
authors.affiliation: INSERM U337, Faculty Broussais-Hotel Dieu, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Samain
authors.forename: H
authors.initials: H
authors.lastname: Bouillier
authors.forename: S
authors.initials: S
authors.lastname: Miserey
authors.forename: C
authors.initials: C
authors.lastname: Perret
authors.forename: J F
authors.initials: JF
authors.lastname: Renaud
authors.forename: M
authors.initials: M
authors.lastname: Safar
authors.forename: G
authors.initials: G
authors.lastname: Dagher
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; D019284:Thapsigargin; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium