Innervation and vascular pharmacodynamics of the mouse spleen

Neurohistochemical and in vivo and electron microscopic methods demonstrated alpha-and beta-adrenergic receptors and adrenergic innervation in arterioles and "arterial" capillaries of the mouse spleen. Such innervation and receptors in venules and channels within the red pulp were sparse. Cholinergic innervation and receptors were judged to be absent in the microvasculature. Histamine elicited arteriolar dilation which was blocked by metiamide suggesting the presence of H2 receptors. However, following blockade of H2 receptors, histamine produced arteriolar constriction. Serotonin elicited only venular constriction. Lactic acid caused arteriolar constriction; bradykinin and prostaglandins (PG) E2 and PGF2 alpha triggered arteriolar constriction, but only at higher concentrations. The vasoconstriction evoked by cholinergic agonists, histamine, lactic acid, or PGs was partially or completely antagonized by alpha-adrenoceptor blockade or by reserpine, and the vasoconstrictor responses to histamine, lactic acid, PGs, bradykinin were enhanced in the presence of functional adrenergic nerves. In the latter case higher doses of phentolamine provoked arteriolar vasospasm. Although adenine nucleotides, guanosine, inosine, sodium phosphate, and sodium chloride elicited no response, adenosine was a potent vasodilator. This dilation was not blocked by beta-adrenergic antagonists, and it was enhanced in the presence of functional adrenergic nerves. The data suggest that: (1) cholinergic agonists, lactic acid, histamine, and PGE2 and PGF2 alpha cause alpha-mediated arteriolar constriction by releasing stored neurotransmitter(s) from splenic nerves, and (2) subthreshold quantities of neurotransmitter(s) may modulate microvascular sensitivity to vasoactive agents which act directly upon the vascular wall.