Vascular relaxation by ifenprodil in the isolated perfused rat mesenteric artery.

The possible mechanism of vascular relaxation by ifenprodil has been examined in the isolated perfused rat mesenteric artery preparation. Ifenprodil (5.0 X 10(-9)-5.0 X 10(-8) M) noncompetitively blocked noradrenaline- and cirazoline-induced vasoconstrictor responses. This concentration range did not affect responses to 5-hydroxytryptamine and potassium chloride. However, in concentrations above 10(-6) M, ifenprodil caused (a) reversal of constrictor responses to excess potassium given either by bolus injections (3.4 X 10(-2)-5.4 X 10(-1) M) or by continuous perfusion (55 mM) and (b) inhibition of Ca2+-induced constrictor effects in arteries perfused with Ca2+-free depolarizing Krebs solution. It is concluded that ifenprodil blocks Ca2+ mobilization through both the ion channels coupled to alpha-adrenoceptors and the potential-sensitive channels.