Vasoactive effects of basic and acidic fibroblast growth factors in hamster cheek pouch arterioles.

Abstract

Fibroblasts growth factors (FGFs) exhibit well-known angiogenic actions, but there is some controversy about whether they have vasoactive effects on blood vessels which might contribute to angiogenesis per se. To clarify this, changes in arteriolar diameter were recorded during observation by videomicroscopy of 3rd- and 4th (terminal)-order arterioles (resting diameters 22.5 +/- 0.5 microns and 14.4 +/- 0.3 microns, respectively) in the hamster cheek pouch in response to FGF application. Recombinant human bFGF (basic) and aFGF (acidic) were applied from micropipettes positioned 5-10 microns from the adventitial surface of vessels. Maximum vasodilator effects of adenosine (10(-4) M) applied in a similar way were also observed. Adenosine increased the diameters of 4th-order arterioles by 37.2 +/- 3.8% and those of 3rd-order arterioles by 38.7 +/- 2.7. bFGF produced vasodilatation (threshold dose 0.1 ng ml-1) in both classes of arterioles, while aFGF produced dose-dependent constriction (threshold dose 0.01 ng ml-1). A maximal dilator effect in 4th-order arterioles was obtained with 100 ng ml-1 bFGF, when diameters reached 82.6 +/- 2.4% of those with adenosine. Maximal constrictor effect (-48.2 +/- 5.6% of resting diameter) occurred with a dose of 100 ng ml-1 aFGF. Vehicle alone (MOPS or bicarbonate buffer used as solvents for FGFs) had no effect. As vasoconstrictors are known to stimulate growth of smooth muscle cells while dilators stimulate growth of endothelial cells, it is possible that the opposing vasoactivities demonstrated for aFGF and bFGF are linked with their selective mitogenicity for smooth muscle and endothelial cells, respectively, and contribute to their angiogenic actions.