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.
Saenz de Tejada
I
I
Departamento de Investigación, Hospital Ramón y Cajal, Carretera de Colmenar, Km. 9.100, Madrid E-28034, Spain.
Carceller
F
F
Fernandez
A
A
Cuevas
B
B
Ortes
L
L
Giménez-Gallego
G
G
Cuevas
P
P
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D004610:Ellagic Acid / Q000494:pharmacology; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D006801:Humans; D007704:Kininogens / Q000172:deficiency; D007705:Kinins / Q000502:physiology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D000959:Antihypertensive Agents; D065168:Bradykinin Receptor Antagonists; D007704:Kininogens; D007705:Kinins; D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; C074544:bradykinin, 1-adamantanecarboxylic acid-Arg(0)-Hyp(3)-Thi(5,8)-Phe(7)-; D004610:Ellagic Acid; D000218:Adamantane; D001920:Bradykinin