Spontaneously hypertensive versus control rat aorta response to neutrophil-derived factors.

We designed experiments to study the interaction of activated rat peritoneal neutrophils with aortas from spontaneously hypertensive rats (SHR) compared with those from normotensive rats. In aortic rings precontracted with phenylephrine, neutrophils obtained from normotensive rats caused a cell number-dependent relaxation of normotensive rat aorta with or without endothelium, whereas relaxation (at lower concentrations) followed by contraction (at higher concentrations) was observed in SHR aorta with endothelium. In SHR aortic rings denuded of endothelium, neutrophils did not induce contraction. The relaxation might be due to a factor indistinguishable from nitric oxide. The contraction might be due to prostaglandin H2 because it was blocked by indomethacin, a cyclooxygenase inhibitor, and ridogrel, a thromboxane A2 synthetase inhibitor/thromboxane A2-prostaglandin H2 antagonist, but not by superoxide dismutase, a superoxide anion scavenger, or dazoxiben, a thromboxane A2 synthetase inhibitor. SHR neutrophils caused a cell number-dependent relaxation of normotensive rat aorta with or without endothelium, whereas relaxation followed by contraction was observed in SHR aorta with endothelium. In SHR aortic rings denuded of endothelium, neutrophils did not induce contraction. The relaxation might be due to a factor indistinguishable from nitric oxide. The contraction seems to be due to superoxide anion because it was inhibitable by indomethacin and superoxide dismutase but not by dazoxiben and ridogrel. Equivalent amounts of superoxide anion were produced by unstimulated and phorbol myristate acetate-stimulated neutrophils obtained from either SHR or normotensive rats. Therefore, increased production of this anion could not explain the contraction observed in hypertensive aortas.(ABSTRACT TRUNCATED AT 250 WORDS)