Angiotensin II increases GABAB receptor expression in nucleus tractus solitarii of rats.
Increasing evidence indicates that both the angiotensin II (ANG II) and gamma-aminobutyric acid (GABA) systems play a very important role in the regulation of blood pressure (BP). However, there is little information concerning the interactions between these two systems in the nucleus tractus solitarii (NTS). In the present study, we examined the effects of ANG II on GABAA and GABAB receptor (GAR and GBR) expression in the NTS of Sprague-Dawley rats. The direct effect of ANG II on GBR expression was determined in neurons cultured from NTS. Treatment of neuronal cultures with ANG II (100 nM, 5 h) induced a twofold increase in GBR1 expression, as detected with real-time RT-PCR and Western blots, but had no effect on GBR2 or GAR expression. In electrophysiological experiments, perfusion of neuronal cultures with the GBR agonist baclofen decreased neuronal firing rate by 39% and 63% in neurons treated with either PBS (control) or ANG II, respectively, indicating that chronic ANG II treatment significantly enhanced the neuronal response to GBR activation. In contrast, ANG II had no significant effect on the inhibitory action of the GAR agonist muscimol. In whole animal studies, intracerebroventricular infusion of ANG II induced a sustained increase in mean BP and an elevation of GBR1 mRNA and protein levels in the NTS. These results indicate that ANG II stimulates GBR expression in NTS neurons, and this could contribute to the central nervous system actions of ANG II that result in dampening of baroreflexes and elevated BP in the central actions of ANG II.
Yao
Fanrong
F
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota, USA.
Sumners
Colin
C
O'Rourke
Stephen T
ST
Sun
Chengwen
C
D000200:Action Potentials; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007263:Infusions, Parenteral; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; C116566:Gabbr2 protein, rat; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D000804:Angiotensin II; D009118:Muscimol; D001418:Baclofen