Kinins are implicated of the hypotensive effect of acidic fibroblast growth factor

Acidic fibroblast growth factor causes an acute and transient nitric oxide-dependent hypotensive effect in experimental animals. However, this response is not found, or is very small, in vitro. We hypothesized that plasma mediators, such as kinins, are involved in aFGF-induced hypotension. We studied the hypotensive effect of intravenous aFGF (1 microg) in control Wistar rats, and compared this response to that in Wistar rats treated with a bradykinin receptor antagonist Na-adamantaneacetyl-D-Arg-(Hyp3,Thi5,8,D-Phe7]-brad yki nin), in kininogen-deficient Brown-Norway-Katholiek (BNK) rats, and in rats depleted of kininogen after repeated treatment with ellagic acid. FGF was administered in the jugular vein and mean arterial pressure was measured through a femoral artery catheter. Following treatment with the bradykinin receptor antagonist, the hypotensive effect of aFGF was reduced 38% with 58 microg of antagonist and by 60% with the 420 microg dose (9 +/- 1 vs 22 +/- 3mm Hg, p<0.01). Mean blood pressure decrease was 12 +/- 1 in BNK rats (p<0.01, vs control) and 10 +/- 2 mm Hg in kininogen-depleted ellagic acid-treated rats (p<0.05, vs control). These findings implicate kinins as necessary mediators for the hypotensive effect of aFGF in vivo. A full hypotensive effect of aFGF requires sufficient amounts of kininogens, the precursor molecules of kinins, as well as bradykinin receptors.