Differential effect of acute angiotensin II type 1 receptor blockade on the vascular and adrenal response to exogenous angiotensin II in humans.
BACKGROUND
Aldosterone stimulation by angiotensin II may not exclusively be mediated by the angiotensin II type 1 (AT(1)) receptor. We have, therefore, investigated the vascular and adrenal response to angiotensin II infusion without and with pretreatment with the AT(1) receptor antagonist valsartan (160 mg).


METHODS
In nine healthy human volunteers, angiotensin II was administered intravenously at doses of 1, 3, and 10 ng/kg/min, each over 45 min. Arterial blood pressure (BP) was measured oscillometrically at 5-min intervals. Blood for the determination of plasma renin activity and aldosterone was taken before the start of the infusion, at the end of each infusion period, and 1 h after the infusion was stopped.


RESULTS
Angiotensin II increased systolic and diastolic BP from 121 +/- 3/70 +/- 2 mm Hg to a maximum of 146 +/- 2/97 +/- 1 mm Hg (P <.001) and plasma aldosterone from 39.2 +/- 9.8 to 290.7 +/- 48.3 (P <.001). The increase in BP after exogenous angiotensin II was completely abolished in volunteers pretreated with valsartan, averaging 118 +/- 3/72 +/- 1 mm Hg by the end of the maximum angiotensin infusion dose. In contrast, plasma aldosterone stimulation by angiotensin II was only partially blunted by concomitant AT(1) receptor blockade (98.9 +/- 16.3 pg/mL after the maximal dose of angiotensin II).


CONCLUSIONS
These results indicate that although the vascular response to exogenous angiotensin II is exclusively mediated by the AT(1) receptor, the effects of angiotensin II on adrenal aldosterone release may involve other pathways.
Lottermoser
Katja
K
Medizinische Universitäts-Poliklinik, Bonn, Germany.
Unger
Thomas
T
Gohlke
Peter
P
Vetter
Hans
H
Düsing
Rainer
R
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects*; D016232:Endothelins / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068756:Valsartan; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D016232:Endothelins; D015850:Interleukin-6; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000450:Aldosterone; D000068756:Valsartan; D012083:Renin; D014633:Valine; D006854:Hydrocortisone