Pressure-induced constriction in cerebral vessels is impaired in a mouse model of systemic lupus erythematosus (NZBWF1)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects females. Up to 75% of patients develop neuropsychiatric symptoms (NPSLE); characterized by cognitive dysfunction, mood disorders and seizures, however the pathogenesis of NPSLE remains unclear. Pressure-induced constriction (PIC) is an intrinsic, mechano-dependent response in certain small arteries and arterioles including those in the brain and kidney. The PIC response has been proposed to play a protective role by preventing transmission of systemic blood pressure to the delicate microvasculature of the kidney and brain, thereby protecting them from barotraumas. Yet, the integrity of the PIC response in cerebral vessels in SLE has never been addressed. Therefore, the purpose of this study was to determine the integrity of the PIC response in middle cerebral arteries (MCA) from a mouse model of SLE. For these studies, we utilized New Zealand Black/White model of SLE using female offspring of NZW x NZB mating (NZBWF1) and NZW control mice. We examined agonist- and pressure-induced vasoconstriction responses. Our results indicate that vasoconstriction in the NZBWF1 to the depolarizing agent KCl and the alpha-adrenergic agonist phenylephrine is unaltered at 10 and 30 weeks of age compared to control NZW mice. In contrast, PIC responses are attenuated by 50% at 10, and totally abolished by 30 weeks of age. Since loss of PIC responses may lead to vascular inflammation and injury, we examined vascular cytokine expression and immune cell infiltration in 20-week-old mice and found increased expression of monocyte chemo-attractants (MCP-1/5, CSF1). Using flow cytometry, we found increased quantities of CD45 + leukocytes, CD11b + myeloid cells, and CD11b + /Ly6G - monocytes/macrophages in cerebral vessel tissues of SLE mice. To determine if loss of the PIC response was associated with vascular injury, we assessed blood brain barrier (BBB) permeability using Evans blue extravasation into brain tissue and found increased permeability. Taken together, these findings indicate progressive PIC impairment in SLE, which leads to vascular inflammation and BBB disruption. Loss of the PIC response by 10 weeks of age precedes the onset of anti-double stranded DNA, endothelial dysfunction, renal disease, and hypertension in the NZBWF1 model, suggesting that loss of the PIC responses may be a causative factor in cardiovascular consequences of SLE. Future studies will examine mechanisms underlying loss of the PIC response in SLE cerebral vessels and protection against NPSLE symptoms. Research supported by: R01 DK137167, P30GM149404, U54HL169191. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.