PMID- 9453333
OWN - NLM
STAT- MEDLINE
DCOM- 19980220
LR  - 20190722
IS  - 0194-911X (Print)
IS  - 0194-911X (Linking)
VI  - 31
IP  - 1 Pt 2
DP  - 1998 Jan
TI  - AT1 and AT2 receptor blockade and epinephrine release during insulin-induced 
      hypoglycemia.
PG  - 384-90
AB  - Angiotensin II facilitates epinephrine release during insulin-induced 
      hypoglycemia, and this effect appears to be independent of type 1 angiotensin II 
      (AT1) receptors in man. In the present study, we hypothesized that the action of 
      angiotensin II on adrenomedullary epinephrine release is mediated by an AT2 
      receptor-dependent mechanism. In conscious chronically instrumented rats, we 
      measured plasma concentrations of catecholamines during acute insulin-induced 
      hypoglycemia in groups of rats pretreated with the AT1 receptor antagonist 
      losartan (10 mg/kg i.v.), the AT2 receptor antagonist PD123319 (30 mg/kg i.v.), 
      combined losartan + PD123319, the converting enzyme inhibitor enalapril (1 mg/kg 
      i.v.), or vehicle. In vehicle-treated rats, the area under the curve for changes 
      in plasma epinephrine concentration [AUC(plasma epinephrine)] during 
      insulin-induced hypoglycemia was 111+/-8 nmolXh/L (+/-SEM). Pretreatment with 
      losartan alone did not affect AUC(plasma epinephrine) (113+/-17 nmol x h/L), 
      while pretreatment with PD123319 tended to reduce the response (87+/-10 nmol x 
      h/L; P=.08 versus vehicle). However, AUC(plasma epinephrine) was significantly 
      reduced in rats that were pretreated with combined losartan + PD123319 (68+/-5 
      nmol x h/L; P<.001 versus vehicle) or enalapril: 86+/-10 nmol x h/L (P<.05 versus 
      vehicle). Thus, combined treatment with losartan + PD 123319 proved more 
      effective in attenuating the reflex increase in plasma epinephrine concentration 
      during hypoglycemia than either of the two AT receptor antagonists given alone. 
      We speculate that angiotensin II through binding to both receptor subtypes 
      facilitates the sympathoadrenal reflex response by actions at several anatomical 
      levels of the neural pathways involved in the sympathoadrenal reflex response 
      elicited during insulin-induced hypoglycemia.
FAU - Worck, R H
AU  - Worck RH
AD  - Department of Pharmacology, University of Copenhagen, Denmark. 
      rene.worck@farmakol.ku.dk
FAU - Frandsen, E
AU  - Frandsen E
FAU - Ibsen, H
AU  - Ibsen H
FAU - Petersen, J S
AU  - Petersen JS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Insulin)
RN  - 0 (Pyridines)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 130663-39-7 (PD 123319)
RN  - 69PN84IO1A (Enalapril)
RN  - JMS50MPO89 (Losartan)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - *Angiotensin Receptor Antagonists
MH  - Angiotensin-Converting Enzyme Inhibitors/pharmacology
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Enalapril/pharmacology
MH  - Epinephrine/*blood
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Hypoglycemia/blood/chemically induced/*physiopathology
MH  - Imidazoles/*pharmacology
MH  - Insulin/*pharmacology
MH  - Kinetics
MH  - Losartan/*pharmacology
MH  - Male
MH  - Pyridines/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1
MH  - Receptor, Angiotensin, Type 2
EDAT- 1998/02/07 00:00
MHDA- 1998/02/07 00:01
CRDT- 1998/02/07 00:00
PHST- 1998/02/07 00:00 [pubmed]
PHST- 1998/02/07 00:01 [medline]
PHST- 1998/02/07 00:00 [entrez]
AID - 10.1161/01.hyp.31.1.384 [doi]
PST - ppublish
SO  - Hypertension. 1998 Jan;31(1 Pt 2):384-90. doi: 10.1161/01.hyp.31.1.384.