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 intercellular adhesion molecule (ICAM)-1 expression by human vascular endothelial cells derived from umbilical cord veins (HUVECs) and plasma soluble ICAM-1 levels in vivo.


RESULTS
Cultured HUVECs were incubated with Ang II (from 10(-9) to 10(-6) mol/L) with or without candesartan and PD12319 (inhibitors of Ang II AT(1) and AT(2) receptors, respectively) for various times up to 4 hours. Total RNA was then extracted from HUVECs, and Northern blots were probed with a 1.9-kb ICAM-1 cDNA fragment. HUVEC supernatants were used to assess 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 increased (P<0. 002) after 2-hour Ang II stimulation. In vivo, Ang II (at an initial 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), losartan (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 normotensives (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 in vitro and in vivo soluble ICAM-1 release. AT(1) receptor blockade inhibits such endothelial effects of Ang II.
Pastore
L
L
University of L'Aquila, Department of Experimental Medicine, Rome, Italy.
Tessitore
A
A
Martinotti
S
S
Toniato
E
E
Alesse
E
E
Bravi
M C
MC
Ferri
C
C
Desideri
G
G
Gulino
A
A
Santucci
A
A
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001262:Atenolol / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects; D014471:Umbilical Veins
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; D001262:Atenolol; D019808:Losartan