Histamine H2 receptor-mediated endothelium-dependent relaxation in canine spinal artery

The mechanisms of histamine-induced relaxation were investigated in isolated canine spinal branches of intercostal artery (SBICA). Histamine (10(-7) to 10(-4)M) and dimaprit (3 x 10(-6) to 3 x 10(-4)M) produced concentration-dependent relaxation in the SBICA which had been contracted by 5 x 10(-6)M norepinephrine, whereas 2-pyridylethylamine caused only a very small relaxation. The histamine- and dimaprit-induced relaxation were inhibited by famotidine but not by diphenhydramine. In the SBICA without endothelium, histamine elicited very little relaxation. Aspirin (5 x 10(-5)M) and AA 861 (10(-5)M) did not affect the histamine-induced relaxation. Treatment with L-NMMA (3 x 10(-5)M) or methylene blue (10(-5)M) significantly suppressed the acetylcholine-induced relaxation of the SBICA but not the histamine-induced one. These results suggest that histamine produces relaxation in the isolated canine SBICA through stimulation of H2-receptors on the endothelium. The relaxing mediator(s) released by histamine seems to be neither endogenous prostaglandins, lipoxygenase products, nor nitric oxide.