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1 Department of Pharmacology, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen N; 2 Department of Medicine M, Glostrup Hospital, University of Copenhagen, DK-2600 Copenhagen; and 3 Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, University of Copenhagen, DK-2600, Copenhagen, Denmark
Simultaneous blockade
of systemic AT1 and AT2 receptors or converting
enzyme inhibition (CEI) attenuates the hypoglycemia-induced reflex
increase of epinephrine (Epi). To examine the role of brain AT1 and AT2 receptors in the reflex regulation
of Epi release, we measured catecholamines, hemodynamics, and renin
during insulin-induced hypoglycemia in conscious rats pretreated
intracerebroventricularly with losartan, PD-123319, losartan and
PD-123319, or vehicle. Epi and norepinephrine (NE) increased 60-and
3-fold, respectively. However, the gain of the reflex increase in
plasma Epi (
plasma Epi/
plasma glucose) and the overall Epi and NE
responses were similar in all groups. The ensuing blood pressure
response was similar between groups, but the corresponding bradycardia
was augmented after PD-123319 (P < 0.05 vs. vehicle)
or combined losartan and PD-123319 (P < 0.01 vs. vehicle). The findings indicate 1) brain
angiotensin receptors are not essential for the reflex regulation of
Epi release during hypoglycemia and 2) the gain of
baroreceptor-mediated bradycardia is increased by blockade of brain
AT2 receptors in this model.
losartan; PD-123319; epinephrine; baroreflex
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O. Skott Renin Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R937 - R939. [Full Text] [PDF] |
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