VASODILATOR RESPONSE OF MESENTERIC ARTERIOLES TO HISTAMINE IN SPONTANEOUSLY HYPERTENSIVE RATS

Recent evidence suggests that spontaneously hypertensive rats (SHR) ex hibit an impaired response to inflammatory mediators. We designed this study to analyze the response of arterioles of SHR after stimulation with a proinflammatory agent, histamine, compared with the response of arterioles of normotensive Wistar-Kyoto (WKY) controls. We observed m esenteric arterioles by intravital microscopy in rats under general an esthesia and measured their lumen diameters after histamine superfusio n. To compare the concentration-response curve with histamine, we also studied the effect of an endothelium-dependent vasodilator: acetylcho line, and an independent vasodilator, sodium nitroprusside. At the end of each experiment we applied papaverine topically to determine the m aximal diameter for each vessel, from which we computed arteriolar ton e. Arteriolar tone in SHR is set at a higher steady state level than i n WKY. The concentration required for a 50% dilator response (EC(50)) of histamine in SHR was significantly higher than that in WKY. In SHR the arteriolar response showed the same refractory pattern to histamin e as to acetylcholine. In contrast, the EC(50) of sodium nitroprusside in SHR was similar to that in WKY. Our results indicate that SHR exhi bit an impaired dilator response to histamine that is due to a blunted endothelium-dependent vasodilation.