Brain angiotensin receptors and sympathoadrenal regulation during insulin-induced hypoglycemia.
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 (Deltaplasma Epi/Deltaplasma 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.
Department of Pharmacology, The Panum Institute Bldg. 18.6, University of Copenhagen, Blegdamsvej. 3, DK-2200 Copenhagen N, Denmark. worck@dadlnet.dk
R H
RH
Worck
D
D
Staahltoft
T E
TE
Jonassen
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E
Frandsen
H
H
Ibsen
J S
JS
Petersen
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007328:Insulin / Q000494:pharmacology*; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan; D009638:Norepinephrine; D004837:Epinephrine