Microcirculatory responses to complement activation are blunted by hypertension.

Abstract

Vasodilation of small arterioles in skeletal muscle during sepsis is an endothelium-dependent response. Renovascular hypertension significantly attenuates this response. Complement activation by zymosan infusion causes small arteriole dilation in skeletal muscle similar to that seen during sepsis. This study was conducted to show whether renovascular hypertension alters the skeletal muscle microcirculatory responses in normotensive rats to systemic activation of the alternative complement system. We found that hypertension abolished the constriction of large A1 arterioles (+3 +/- 2% change at 45 min) and dilation of small A4 arterioles (-2 +/- 2% change at 45 min) in skeletal muscle. Hypertension attenuated but did not abolish (A4: +70 +/- 13% change in hypertensive vs +111 +/- 18% in normotensive rats) the ability of small arterioles to dilate to nitroprusside, an endothelium-independent vasodilator. This suggest that hypertension modifies some type of receptor-level mechanism to reduce small arteriolar dilation during complement activation. We next used hydroquinone to topically block endothelium-derived relaxing factor (EDRF) in hypertensive animals whose complement systems were activated. Hydroquinone did not change the response of large A1 arterioles (+5 +/- 4% hydroquinone change vs +3 +/- 2% non-hydroquinone at 45 min) to complement activation. However, hydroquinone allowed construction of small A4 arterioles (-12 +/- 5% hydroquinone change vs -2 +/- 2%, non-hydroquinone at 45 min) during complement activation in hypertensive rats. We conclude that during hypertension the release of EDRF in small arterioles after complement activation is counterbalanced by a constrictor-producing mechanism.