Dual influence of hydralazine on constrictor response to noradrenaline in isolated arterial smooth muscle

The effects of hydralazine (Hyd) on vascular smooth muscle contractile response to alpha-receptor stimulation by exogeneous and endogenous noradrenaline (NA) in the absence and presence of Mg2+ (1.2 mM) were examined using a proximal segment of rabbit's ear artery. Intraluminal perfusion with Hyd (2 x 10(-4) M) in normal Krebs bicarbonate mediuim inhibited the NA-induced contraction only in the presence of Mg2+ (1.2 mM) in the medium. The extraluminal superfusion of the artery with Hyd (2 x 10(-4) M) enhanced the vasoconstriction to extraluminally superfused NA in either the presence or absence of Mg2+ in the medium. However, when the artery was preincubated with an adrenergic neuron blocker, guanethidine (3.2 x 10(-6) M), Hyd (2 x 10(-4) M) inhibited NA-induced vasoconstriction. Contrary to the effects of Hyd on intraluminal NA, Hyd potentiated the response of this superfused artery to electrical stimulation in the presence of Mg2+ (1.2 mM) whereas in the Mg2+-free medium, it inhibited the constriction. These findings suggest that Hyd may have dual effects on isolated vascular smooth muscle by directly inhibiting the contractile activation and indirectly by an interference at adrenergic nerves, which potentiates the effects of exogenous NA and(or) alters the release of endogenous NA.