Peripheral blood mononuclear cell CD62L and CD11a expression and soluble interstitial cell adhesion molecule-1 levels following infused isoproterenol in hypertension.
OBJECTIVE
Increasingly, studies indicate that alterations in leukocyte and endothelial cell adhesion molecules may enhance atherosclerotic processes in human hypertension. beta-adrenergic receptor activation has long been implicated in the aetiology and/or maintenance of hypertension and also has significant effects on leukocyte and endothelial adhesion molecules. This study therefore examined the effects of hypertension on peripheral blood mononuclear cell CD62L and CD11a expression and circulating soluble interstitial cell adhesion molecule (ICAM)-1 (sCD54) levels following infusion of the non-specific beta-adrenergic agonist isoproterenol.


METHODS
In the setting of a General Clinical Research Center, 15 hypertensive and 20 normotensive subjects underwent an infusion of isoproterenol consisting of two sequential 15 min fixed-order doses of 20 and 40 ng/kg per min. Flow cytometry was used to quantify lymphocyte and monocyte populations and adhesion molecules, and ELISA was used to quantify sCD54 levels.


RESULTS
As expected, isoproterenol led to a significant increase in the number of circulating lymphocytes (P < 0.001) and monocytes (P < 0.01). The number of circulating CD3+CD8+CD62Llow T cytotoxic cells increased following isoproterenol (P < 0.001) and this increase was greater in hypertensives than in normotensives (P < 0.05). Isoproterenol led to a decrease in surface density of CD62L (P < 0.001) and an increase in surface density of CD11a (P < 0.001) in all subjects. Hypertensives had a significantly lower CD62L density (P = 0.01) and higher CD11a density on lymphocytes (P = 0.002) compared to normotensives. sCD54 levels were unchanged following isoproterenol but were elevated in hypertensives (P < 0.05).


CONCLUSIONS
A beta-adrenergic-induced environment of increased CD62Llow/CD11ahigh leukocytes, coupled with existing endothelial CD54 activation, could support basic atherosclerotic processes of increased peripheral blood mononuclear cell-endothelial adhesion in hypertension.
Mills
Paul J
PJ
Department of Psychiatry, University of California, San Diego, La Jolla, California, USA. pmills@ucsd.edu
Farag
Noha H
NH
Perez
Christy
C
Dimsdale
Joel E
JE
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects*; D007545:Isoproterenol / Q000627:therapeutic use*; D019041:L-Selectin / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000097:blood*; D008297:Male; D012995:Solubility / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D007545:Isoproterenol