SPONTANEOUSLY HYPERTENSIVE VERSUS CONTROL RAT AORTA RESPONSE TO NEUTROPHIL-DERIVED FACTORS

We designed experiments to study the interaction of activated rat peri toneal neutrophils with aortas from spontaneously hypertensive rats (S HR) compared with those from normotensive rats. In aortic rings precon tracted with phenylephrine, neutrophils obtained from normotensive rat s caused a cell number-dependent relaxation of normotensive rat aorta with or without endothelium, whereas relaxation (at lower concentratio ns) followed by contraction (at higher concentrations) was observed in SHR aorta with endothelium. In SHR aortic rings denuded of endotheliu m, neutrophils did not induce contraction. The relaxation might be due to a factor indistinguishable from nitric oxide. The contraction migh t be due to prostaglandin H-2 because it was blocked by indomethacin. a cyclooxygenase inhibitor, and ridogrel, a thromboxane A(2) synthetas e inhibitor/thromboxane A(2)-prostaglandin H-2 antagonist, but not by superoxide dismutase, a superoxide anion scavenger, or dazoxiben, a th romboxane A(2) synthetase inhibitor. SHR neutrophils caused a cell num ber-dependent relaxation of normotensive rat aorta with or without end othelium, whereas relaxation followed by contraction was observed in S HR aorta with endothelium. In SHR aortic rings denuded of endothelium, neutrophils did not induce contraction. The relaxation might be due t o a factor indistinguishable from nitric oxide. The contraction seems to be due to superoxide anion because it was inhibitable by indomethac in and superoxide dismutase but not by dazoxiben and ridogrel. Equival ent amounts of superoxide anion were produced by unstimulated and phor bol myristare acetate-stimulated neutrophils obtained from either SHR or normotensive rats. Therefore, increased production of this anion co uld not explain the contraction observed in hypertensive aortas. In co nclusion, our data might indicate a role for neutrophils in the elevat ed peripheral vascular resistance in hypertension because an endotheli um-dependent contraction was induced by neutrophils in vessels of hype rtensive rats.