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(Hypertension. 2000;35:61.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Extracellular Signal-Regulated Kinase Pathway Is Involved in Basic Fibroblast Growth Factor Effect on Angiotensin II–Induced Ca²⁺ Transient in Vascular Smooth Muscle Cell From Wistar-Kyoto and Spontaneously Hypertensive Rats

Emmanuel Samain; Hélène Bouillier; Stéphanie Miserey; Claudine Perret; Jean-François Renaud; Michel Safar; Georges Dagher

From INSERM U337 (E.S., H.B., C.P., M.S., G.D.), Faculty Broussais-Hotel Dieu, Paris, France; INSERM U36 (S.M.), Collège de France, Paris, France; and CNRS (J.-F.R.), Marie Lannelongue Hospital, Department of Medical Research, Le Plessis Robinson, France.

Correspondence to Dr Michel Safar, Hopital Broussais, Service de Médecine Interne 1.0, 96 rue Didot, 75014 Paris, France.

Abstract—We studied the effect of basic fibroblast growth factor (b-FGF) on different Ca²⁺ mechanisms elicited by angiotensin II (Ang II) in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Intracellular Ca²⁺ (Ca²⁺_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. Ca²⁺_i was assessed in Fura-2–loaded cells with fluorescent imaging microscopy. Ang II subtype 1 receptor activation by Ang II (1 µmol/L) induced a transient increase in Ca²⁺_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 Ca²⁺_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 Ca²⁺ influx in both strains. Similar results were observed when Ca²⁺ 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 Ca²⁺ 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.

Key Words: fibroblast growth factor • angiotensin II • muscle, smooth, vascular • calcium • kinase • hypertension, genetic