Relaxation of isolated rabbit arteries by fusaric (5-butylpicolinic) acid.

The influence of fusaric (5-butylpicolinic) acid on vascular contractile or relaxing response was examined in different isolated arterial preparations of the rabbit. Prior exposure (10 minutes) to 1 x 10(-4) to 1 x 10(-3) M fusaric acid decreased contractile responses elicited with norepinephrine, histamine, serotonin, acetylcholine, angiotensin II and KCl in helical strips of rabbit aorta and superior mesenteric, carotid, renal, and femoral arteries. Fusaric acid produced a shift to the right and down in the dose-response curves to all tested agonists, and antagonized acetylcholine and serotonin most effectively among these agonists. These results indicate that fusaric acid antagonized nonspecifically these contractile agonists. When blood vessels were contracted with prostaglandin F2alpha, fusaric acid caused relaxation of rabbit aorta and superior mesenteric, carotid, renal, and femoral arteries in a dose-dependent fashion. Among blood vessels tested superior mesenteric arteries were relaxed the most effectively by fusaric acid. The concentration of fusaric acid which induced 50% relaxation of aortic strips was about 10-fold higher than that of papaverine. Propranolol and atropine did not affect fusaric acid-induced relaxation, suggesting that fusaric acid did not work through beta adrenergic or cholinergic receptors. Ethylene glycol bis(beta-aminoethyl-ether)-N,N'-tetraacetic acid which chelates with Ca++ caused blood vessel relaxation in doses similar to those of fusaric acid. As fusaric acid is known to chelate Ca++, a possible mechanism of fusaric acid to relax blood vessel through Ca++ depletion is discussed briefly.