Glucocorticoid sensitivity of circulating monocytes in essential hypertension.
BACKGROUND
Essential hypertension ranks among the strongest cardiovascular risk factors. Cytokine production by monocytes plays a key role in atherosclerosis development and acute coronary syndromes. We investigated whether stimulated monocyte cytokine release and its inhibition by glucocorticoids would differ between hypertensive and normotensive subjects.


METHODS
Study participants were 222 middle-aged male employees with industrial jobs. Following the criteria of the World Health Organization/International Society for Hypertension, 76 subjects were classified as being hypertensive (systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg). In vitro monocyte tumor necrosis factor (TNF)-alpha release after lipopolysaccharide (LPS) stimulation was assessed with and without coincubation with incremental doses of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting TNF-alpha release by 50%.


RESULTS
Hypertensive subjects showed 11% higher LPS-stimulated TNF-alpha release than normotensive subjects (F(1,181)= 5.21, P =.024). In hypertensive subjects, monocyte glucocorticoid sensitivity was 21% lower than in normotensive subjects (F(1,178)= 4.94, P =.027), indicating that dexamethasone inhibited relatively less TNF-alpha release in hypertensive subjects. Results held significance when a set of classic cardiovascular risk factors was controlled for.


CONCLUSIONS
The findings suggest that proinflammatory activity of circulating monocytes is higher in hypertensive than in normotensive men, providing one potential pathway to explain the increased atherosclerotic risk with essential hypertension.
Wirtz
Petra H
PH
Institute for Behavioral Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland.
von Känel
Roland
R
Frey
Karl
K
Ehlert
Ulrike
U
Fischer
Joachim E
JE
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D015999:Multivariate Analysis; D012307:Risk Factors; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D016207:Cytokines; D005938:Glucocorticoids; D006442:Glycated Hemoglobin; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha