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AT1 receptor blockade and the sympathoadrenal response to insulin-induced hypoglycemia in humans
R H Worck1, H Ibsen, E Frandsen
1Department of Medicine C, University of Copenhagen, Denmark.
Abstract:
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.
Insights
Angiotensin II's role in adrenal catecholamine release was studied during hypoglycemia. AT1 receptor blockade did not alter epinephrine or norepinephrine release, suggesting the interaction isn't mediated by AT1 receptors in humans.
Area of Science:
- Endocrinology
- Neuroscience
- Cardiovascular Physiology
Background:
- Angiotensin II facilitates adrenal catecholamine release across species.
- The specific role of the AT1 receptor in this interaction during human hypoglycemia is not fully understood.
Purpose of the Study:
- To investigate the effect of AT1 receptor blockade on medullary epinephrine and musculocutaneous norepinephrine release during insulin-induced hypoglycemia in humans.
- To determine if the sympathoadrenal response to hypoglycemia is mediated via AT1 receptors.
Main Methods:
- 16 healthy volunteers received either losartan (AT1 receptor blocker) or placebo.
- An intravenous insulin bolus was administered to induce hypoglycemia.
- Measurements of catecholamines, hormones, and cardiovascular parameters were taken over 150 minutes.
Main Results:
- AT1 receptor blockade effectively increased renin and angiotensin II levels, inhibited aldosterone, and decreased mean arterial pressure.
- Insulin-induced hypoglycemia led to a 23-fold increase in epinephrine and a 4-fold increase in norepinephrine release.
- These sympathoadrenal responses, including heart rate and blood flow changes, were independent of AT1 receptor blockade.
Conclusions:
- The facilitating effect of angiotensin II on adrenal catecholamine release during human hypoglycemia is not mediated by AT1 receptors.
- This suggests an alternative pathway for angiotensin II interaction with the sympathoadrenal axis in humans.