PMID- 19426765
OWN - NLM
STAT- MEDLINE
DCOM- 20090918
LR  - 20131121
IS  - 1873-1686 (Electronic)
IS  - 0167-0115 (Linking)
VI  - 156
IP  - 1-3
DP  - 2009 Aug 7
TI  - Cardiovascular effects of ghrelin antagonist in conscious rats.
PG  - 72-6
LID - 10.1016/j.regpep.2009.04.016 [doi]
AB  - Ghrelin, a 28 aa growth-hormone-releasing peptide, has been shown to increase 
      food intake and decrease arterial pressure in animals and in humans. Recently, a 
      ghrelin antagonist (GhA), [d-Lys-3]-GHRP-6, was demonstrated to decrease food 
      intake in mice, but its cardiovascular actions have not been described. In the 
      present study, the effects of the GhA on cardiovascular parameters in conscious 
      rats were investigated and the involvement of the sympathetic nervous system 
      evaluated. Mean arterial pressure (MAP) and heart rate (HR) measurements were 
      assessed by radiotelemetry. GhA was administered in doses of 2, 4 and 6 mg/kg 
      subcutaneously (s.c.). MAP as well as HR was dose-dependently elevated after sc 
      application of GhA. Sympathetic blockade of alpha-adrenoreceptors with 
      phentolamine (3 mg/kg, s.c.) and simultaneous antagonism of 
      beta(1)-adrenoreceptors with atenolol (10 mg/kg, s.c.) abolished the increase in 
      MAP and HR induced by GhA (4 mg/kg, s.c.). Administration of phentolamine alone 
      inhibited the increase of MAP, but not HR; atenolol alone abolished the elevation 
      of both MAP and HR evoked by GhA. These results suggest that the peripheral 
      injection of ghrelin antagonist increases arterial pressure and heart rate, at 
      least in part, through the activation of the sympathetic nervous system. 
      Therefore, the use of the ghrelin antagonist system as a therapeutic target for 
      reduction in food intake might lead to serious side effects like elevated blood 
      pressure in humans mostly already having an elevated blood pressure as part of 
      their metabolic syndrome.
FAU - Vlasova, Maria A
AU  - Vlasova MA
AD  - Department of Pharmaceutics, University of Kuopio, Kuopio, Finland. 
      maria.vlasova@uku.fi
FAU - Jarvinen, Kristiina
AU  - Jarvinen K
FAU - Herzig, Karl-Heinz
AU  - Herzig KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090506
PL  - Netherlands
TA  - Regul Pept
JT  - Regulatory peptides
JID - 8100479
RN  - 0 (Adrenergic alpha-Antagonists)
RN  - 0 (Adrenergic beta-1 Receptor Antagonists)
RN  - 0 (GHRP-6, Lys(3)-)
RN  - 0 (Ghrelin)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Adrenergic, alpha)
RN  - 50VV3VW0TI (Atenolol)
RN  - Z468598HBV (Phentolamine)
SB  - IM
MH  - Adrenergic alpha-Antagonists/pharmacology
MH  - Adrenergic beta-1 Receptor Antagonists
MH  - Animals
MH  - Atenolol/pharmacology
MH  - Blood Pressure/drug effects
MH  - Cardiovascular System/*drug effects
MH  - *Consciousness
MH  - Ghrelin/*antagonists & inhibitors
MH  - Heart Rate/drug effects
MH  - Male
MH  - Oligopeptides/*pharmacology
MH  - Phentolamine/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Adrenergic, alpha/metabolism
MH  - Sympathetic Nervous System/drug effects
EDAT- 2009/05/12 09:00
MHDA- 2009/09/19 06:00
CRDT- 2009/05/12 09:00
PHST- 2008/12/18 00:00 [received]
PHST- 2009/04/24 00:00 [revised]
PHST- 2009/04/29 00:00 [accepted]
PHST- 2009/05/12 09:00 [entrez]
PHST- 2009/05/12 09:00 [pubmed]
PHST- 2009/09/19 06:00 [medline]
AID - S0167-0115(09)00089-5 [pii]
AID - 10.1016/j.regpep.2009.04.016 [doi]
PST - ppublish
SO  - Regul Pept. 2009 Aug 7;156(1-3):72-6. doi: 10.1016/j.regpep.2009.04.016. Epub 
      2009 May 6.