Lack of flow mediated dilation and enhanced angiotensin II-induced constriction in skeletal muscle arterioles of lupus-prone autoimmune mice

Abstract

Systemic lupus erythematosus (SLE) is associated with disturbances in the microcirculation of various tissues, yet the nature of arteriolar dysfunction has not been characterized. Thus, changes in diameter of isolated, pressurized skeletal muscle arterioles of mice with systemic autoimmune disease (lupus prone, MRL/lpr four-month old female) and control (MRL) mice were investigated by video-microscopy. Arteriolar responses to changes in intraluminal pressure, flow, and to vasoactive agents with known mechanisms of action were compared. The active and passive (in Ca²⁺ free solution) diameter of MRL/lpr arterioles were not significantly different compared to MRL and morphometric changes were not apparent. Compared to MRL mice the endothelium-dependent dilations to increase in flow, acetylcholine and bradykinin were markedly reduced in arterioles of MRL/lpr mice. Endothelium-independent dilations to sodium-nitroprusside and adenosine were similar in MRL and MRL/lpr arterioles. Furthermore, angiotensin II elicited greater constrictions in MRL/lpr arterioles, whereas serotonin-induced constrictions were similar in both groups. Thus, in arterioles of MRL/lpr mice endothelium-dependent dilator mechanisms are impaired and constriction to angiotensin II is enhanced, suggesting specific alterations in the vasomotor function of microvessels that are likely contribute to the disturbance of skeletal muscle blood flow observed in systemic lupus erythematosus.

Keywords

angiotensin II endothelium flow-mediated dilation isolated arteriole systemic lupus erythematosus

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