Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo

Background-We evaluated whether angiotensin II (Ang II) influenced intercel lular adhesion molecule (ICAM)-1 expression by human vascular endothelial c ells derived from umbilical cord veins (HUVECs) and plasma soluble ICAM-1 l evels in vivo. Methods and Results-Cultured HUVECs were incubated with Ang II (from 10(-9) to 10(-6) mol/L) with or without candesartan and PD12319 (inhibitors of An g II AT(1) and AT(2) receptors, respectively) for various times up to 4 hou rs. Total RNA was then extracted from HUVECs, and Northern blots were probe d with a 1.9-kb ICAM-1 cDNA fragment. HUVEC supernatants were used to asses s soluble ICAM-1 release by ELISA. Northern blot analysis detected a strong increase of ICAM-1 mRNA after 2-hour incubation with Ang II, The response was inhibited by candesartan, Soluble ICAM-1 release by HUVECs also increas ed (P<0.002) after 2-hour Ang Ii stimulation, In vivo, Ang II (at an initia l rate of 1.0 ng . kg(-1) . min(-1), to be increased each 30 minutes by 2.0 ng . kg(-1) . min(-1) to the final rate of 7.0 ng . kg(-1) . min(-1)) was infused in 8 normotensive and 12 essential hypertensive individuals. In the latter, Ang II was reinfused after 4 weeks on either placebo (n=3), losart an (50 mg UID, n=5), or atenolol (50 mg UID, n=4) treatment. Plasma soluble ICAM-1 levels increased after Ang II infusion in hypertensives and normote nsives (P<0.0001 after 90 minutes). Losartan reduced baseline soluble ICAM- 1 levels (P<0.05) and Ang II-related ICAM-1 increments. Conclusions-Ang II upregulates ICAM-1 expression by HUVECs and stimulates i n vitro and in vivo soluble ICAM-1 release. AT(1) receptor blockade inhibit s such endothelial effects of Ang IT.