AT1 receptor blockade and the sympathoadrenal response to insulin-induced hypoglycemia in humans.
An important facilitating effect of angiotensin II on adrenal catecholamine release has been demonstrated in several species. To determine whether specific AT1 receptor blockade affects medullary epinephrine secretion and musculocutaneous norepinephrine release during insulin-induced hypoglycemia, 16 healthy volunteers received losartan vs. placebo followed by an intravenous insulin bolus and measurement of effect variables at short intervals for 150 min. AT1 receptor blockade was effective, as evidenced by substantially increased circulating renin and angiotensin II levels, a 60% inhibition of circulating aldosterone, and an 8.5% decrease of mean arterial pressure over time compared with placebo. Arterial glucose concentration fell to a nadir of 1.9 mM, arterial epinephrine concentration increased 23-fold, forearm musculocutaneous norepinephrine release increased 4-fold, heart rate increased 40%, and forearm blood flow increased 3-fold. All absolute values and the time course of these changes were independent of AT1 receptor blockade. It is concluded that a putative interaction between angiotensin II and the sympathoadrenal axis may not be mediated by AT1 receptors in humans.
Worck
R H
RH
Department of Medicine C, University of Copenhagen, Denmark.
Ibsen
H
H
Frandsen
E
E
Dige-Petersen
H
H
D000313:Adrenal Medulla / Q000502:physiology*; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D044140:Receptor, Angiotensin, Type 1; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D013564:Sympathetic Nervous System / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D001786:Blood Glucose; D002395:Catecholamines; D007093:Imidazoles; D007328:Insulin; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin; D019808:Losartan