Published online before print December 13, 2001, doi: 10.1161/hh0102.103611
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Submitted on October 5, 2001
Revised on November 13, 2001
Accepted on December 3, 2001
FGF2 Signaling Is Required for the Development of Neuronal Circuits Regulating Blood Pressure
From the Department of Developmental Biology (R.D., A.G., A.Z., R.Z.), Faculty of Biology, Utrecht University, Utrecht, The Netherlands; Institut für Physiologie (J.F., T.V., H.E.), Universität Hamburg, Martinistraße 52, D-20246 Hamburg, Germany; and European Molecular Biology Laboratories (G.T.), Heidelberg, Germany. Present address for G.T. is the Department of Pharmacology, Pharmacia and Upjohn, Nerviano, Italy.
* To whom correspondence should be addressed. E-mail: r.dono{at}bio.uu.nl.
Fibroblast growth factor 2 (FGF2) signaling is involved in angiogenesis, vascular contractility, and cardiac hypertrophy. Mice lacking a functional FGF2 gene (FGF2-/-) are hypotensive, but the primary physiological role of FGF2 in cardiovascular homeostasis remained unknown. Using a chicken FGF2 (cFGF2) transgene under control of the Wnt-1 promotor, we selectively re-expressed FGF2 in the developing nervous system of FGF2-/- (transgenic FGF2 mutant) embryos. Expression of the cFGF2 transgene in the developing nervous system, including its autonomic region, was limited to the period between embryonic day 9.5 and 14.5. Significantly, no FGF2 re-expression was detected in developing heart and blood vessels. Pharmacological analysis revealed a normalization of the blood pressure response to isoproterenol-induced vasodilation in adult transgenic FGF2 mutant mice. In addition, the hypotensive phenotype was rescued in 1 line (of 2) transgenic FGF2 mutant adult mice having expressed higher levels of cFGF2 proteins during nervous system development. These genetic studies indicate that FGF2 signaling is essential for complete development of the neural circuitry required for central regulation of blood pressure, whereas it appears dispensable for blood pressure control in the healthy adult.
Key words: blood pressure • fibroblast growth factor 2 • hypotension • mouse • transgenic
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