Hypertension in cafeteria-fed rats: alterations in renal alpha2-adrenoceptor subtypes.
Obesity is a major cause of human essential hypertension and there are clear evidences that abnormal kidney functions play a key role in obesity hypertension. Feeding rats a cafeteria diet has been extensively used as an experimental model to study obesity and energy balance expenditure. The present study investigated whether rats fed a cafeteria diet develop hypertension with alterations in renal alpha2-adrenoceptor subtype distribution. Weight gain induced by feeding rats a cafeteria diet during 8 weeks was associated with a marked increase in blood pressure. Insulin levels were higher in these hypertensive rats, leading to a decreased plasma glucose/insulin ratio. Based on radioligand-binding studies using [3H]-RX821002 and selective competitors, a raise in alpha2-adrenoceptor density that was solely due to an increased alpha2B-adrenoceptor subtype density was detected in the kidney of the cafeteria-fed rat. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) experiments showed an overexpression of the gene encoding the alpha2B-adrenoceptor subtype in these rats. On the other hand, despite a similar mRNA level, the alpha2A-adrenoceptor subtype was no more detectable by radioligand-binding studies in the kidney of the cafeteria-fed rat. In conclusion, cafeteria-fed rats are hypertensive, with renal alterations in alpha2-adrenoceptor distribution. These alterations, which are not related to genetic factors, may play a key role in the onset of hypertension.
Coatmellec-Taglioni
G
G
Department of Biochemistry and Molecular Biology, Faculté de Médecine de Paris-Ouest, Université René Descartes, CJF INSERM 94-02, Paris, France.
Dausse
J P
JP
Ribière
C
C
Giudicelli
Y
Y
D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure; D004032:Diet / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C547768:ADRA2A protein, human; C547771:ADRA2B protein, human; C547770:Adra2a protein, rat; C547773:Adra2b protein, rat; D015415:Biomarkers; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2