Altered microvascular responses to C5a in rat striated muscle during two-kidney, one clip renovascular hypertension

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ObjectiveTo determine how two-kidney, one clip (2-K,1 C) renovascular hypertension alters microvascular responses in rat striated muscle to complement C5a, one of the most important inflammatory mediators.Methods2-K,1C hypertension was induced in male Sprague-Dawley rats. Under anesthesia with pentobarbital (50 mg/kg, intraperitoneally) the cremaster muscle microcirculatory preparation with intact neurovascular connections was studied in vivo by closed-circuit videomicroscopy. Recombinant human C5a was applied topically in the tissue bath at concentrations of 10-12 or 10-10 and 10-8mol/l, consecutively. Changes in the microvessel diameters in small arterioles, large arterioles and venules were measured.ResultsIn normotensive rats complement C5a induces a significant dilation in small arterioles at low bath concentrations (10-12 or 10-10mol/l), but the dilation is attenuated at a higher concentration (10-8mol/1). In contrast, in 2-K,1C hypertensive rats C5a constricts small arterioles at a low concentration (10-12 or 10-10mol/1) but the dilates them at a higher concentration (10-8 mol/l). Large arterioles and venules have minimal responses to C5a in either normotensive or 2-K, 1C hypertensive rats.Conclusion2-K, 1C hypertension dramatically alters C5a-induced microvascular responses in small arterioles. The alteration might be attributable to the enhanced vasoconstrictor mechanisms and impaired vasodilator mechanisms during 2-K, 1C renovascular hypertension.

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