Effects of xylamine on vascular neuroeffector transmission.

The effect of xylamine on sympathetic neuroeffector transmission in rabbit isolated blood vessels was examined. Xylamine (10(-8) to 10(-6) M) caused a slowly progressing inhibition of the contractions of pulmonary artery evoked by electrical field stimulation. The inhibition was irreversible. Cocaine (3 x 10(-5) M) prevented the inhibitory action of xylamine (10(-7) M), but it did not reverse the inhibition caused by xylamine (10(-6) M). Xylamine (10(-7) to 3 x 10(-5) M) reduced the accumulation of [3H]norepinephrine (NE) (10(-8) M). In the presence of desipramine (10(-6) M), xylamine (10(-7) to 3 x 10(-5) M) and corticosterone (10(-6) to 10(-4)) reduced the 3H-accumulation. Xylamine (10(-7) to 10(-5) M) reduced the tissue NE content by up to 50%. Xylamine (10(-7) to 10(-6) M) antagonized in a noncompetitive manner the contractions of aorta evoked by NE (10(-9) to 3 x 10(-5) M), histamine (10(-6) to 3 x 10(-4) M) and 5-hydroxytryptamine (10(-8) to 3 x 10(-4) M). In the case of NE, the antagonism was more marked in the presence of either cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M) or corticosterone (4 x 10(-5) M). In the presence of xylamine (10(-7) to 10(-6) M), cumulative addition of near maximally effective concentrations of NE, 5-hydroxytryptamine and histamine caused a progressive and complete relaxation of aorta. Xylamine (10(-7) to 10(-5) M) did not alter the contractions of aorta evoked by potassium (17-55 mM). The results support the contention that xylamine is an inhibitor of neuronal and extraneuronal uptake, an adrenergic neurone blocking agent and a noncompetitive antagonist of alpha-1 adrenoceptors, histamine and 5-hydroxytryptamine2 receptors. Xylamine is not a direct acting vasodilator on smooth muscle.