[Effects of angiotensin II on inflammation mediators in healthy subjects].
OBJECTIVE
Inflammatory reactions mediated by cytokines play a central role in the development of atherosclerotic vascular changes. Numerous experimental studies have suggested a connection between the renin-angiotensin-aldosterone system and cytokine liberation from endothelium. This study investigated the effect of exogenous angiotensin II on cytokine liberation in healthy subjects.


METHODS
Nine healthy men, aged 25-28 years, having given informed consent, were given angiotensin II infusions of 1, 3 and 10 ng/kg/min, each time over 45 min, once with and once without preceding oral intake of an AT (1)-receptor antagonist (160 mg valsartan). Arterial blood pressures were measured oscillometrically every 5 min. Blood was taken at the end of each perfusion period and one each after its end, measurements being made of plasma activity of angiotensin II, aldosterone, and the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and the vascular cell adhesion molecule (VCAM)-1.


RESULTS
Plasma angiotensin II concentrations during perfusion rose from 14.7 +/- 16.5 pg/ml to 200.1 +/- 127.2 pg/ml (p< 0.001). The plasma concentrations of angiotensin II were again within the basal range (16.3 +/- 24.8 pg/ml) one hour after the end of perfusion. Angiotensin II raised the systolic and diastolic blood pressure from 121 +/- 9/70 +/- 6 mmHg to a maximum of 146 +/- 6/97 +/- 3 mmHg (p<0.001). This blood pressure rise was prevented by prior administration of the AT (1)-receptor antagonist. Neither the angiotensin II infusion nor the simultaneous administration of AT (1)-antagonist altered the circulating plasma level of TNF-alpha, IL-6 or VCAM-1.


CONCLUSIONS
Increased circulating plasma levels of angiotensin II induce a significant rise in arterial pressure of healthy male subjects, but do not in the short therm produce a change in the plasma levels of the cytokines TNF-alpha, IL-6 and VCAM-1. These results in healthy subjects throw doubt on the hypothesis that, at least in the short term, the effect of angiotensin II on changes in those cytokines measured in this study are independent of the blood pressure.
Lottermoser
K
K
Medizinische Universitäts-Poliklinik, Bonn. katlori@hotmail.com
Ulrich-Merzenich
G
G
Vetter
H
H
Düsing
R
R
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D000450:Aldosterone; D000068756:Valsartan; D014633:Valine