Impaired endothelium‐dependent vasorelaxation contributes to hypertension in leukocyte‐specific protein 1 (LSP1)‐deficient mice

Abstract

LSP1 is an intracellular, Ca2+‐and F‐actin‐binding protein expressed in leukocytes and endothelial cells. Adult male LSP1‐deficient (Lsp1−/−) mice had higher blood pressure than their WT counterparts. By Western blot, LSP1 was found present in aorta and mesenteric artery tissues in WT mice but not in Lsp1−/− mice. The role of LSP1 in regulating arterial vascular tone was studied. The contraction of aorta and mesenteric arteries in response to phenylephrine and angiotensin II was similar in WT and Lsp1−/− mice. The relaxation of aorta artery was more sensitive to sodium nitroprusside and methacholine in Lsp1−/− mice than in WT mice. The phenylephrine‐constricted mesenteric arteries showed identical relaxation curve to sodium nitroprusside in these two strains of mice, but had no relaxation to methacholine in Lsp1−/− mice or in denuded WT mesenteric arteries. Methacholine‐induced mesenteric arterial relaxation in WT mice was suppressed partially by the pretreatment of L‐NAME or the combination of apamin + TRAM‐34, abolished completely by the combination of L‐NAME + apamin + TRAM‐34, but not changed by indomethacin. Our results demonstrate the defects in endothelium‐dependent vasorelaxation in resistance arteries in mice deficient in LSP1 revealing an important role for LSP1 in endothelium‐dependent vasodilation in small resistance arteries and blood pressure regulation.