Angiotensin II enhances GABA(B) receptor-mediated responses and expression in nucleus tractus solitarii of rats.
Angiotensin II (ANG II) increases GABA(B) receptor expression in neuronal cultures from the nucleus tractus solitarii (NTS). In the present study, the chronic effects of ANG II on GABA(B) receptor expression and activity were examined in the NTS of Sprague-Dawley rats. Intracerebroventricular infusion of ANG II caused a significant elevation in blood pressure (BP) and an increase in GABA(B) receptor expression in the NTS. Conversely, chronic N(G)-nitro-l-arginine methyl ester (l-NAME) treatment also increased BP, but had no effect on GABA(B) receptor expression in the NTS. Next, we examined the BP response to the GABA(B) receptor agonist baclofen microinjected into the NTS of ANG II- or artificial cerebrospinal fluid (aCSF)-infused rats. NTS microinjection of baclofen increased BP in both groups of rats. However, the pressor response to baclofen was enhanced in ANG II-infused rats compared with aCSF-infused rats. In addition, bilateral microinjection of the GABA(B) receptor antagonist CGP-35348 into the NTS evoked a decrease in BP in both group of rats, and the depressor responses to CGP-35348 were enhanced in the ANG II-infused rats. In contrast, the pressor responses to the GABA(A) receptor agonist muscimol and the depressor responses to the GABA(A) receptor antagonist bicuculline were comparable between aCSF- and ANG II-infused rats. These results indicate that chronic ANG II infusion stimulates GABA(B) receptor expression and augments GABA(B) receptor-mediated responses in the NTS. This effect could contribute to the central nervous system actions of ANG II that result in dampening of baroreflexes and elevation in arterial BP.
Zhang
Qi
Q
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND 58105, USA.
Yao
Fanrong
F
O'Rourke
Stephen T
ST
Qian
Steven Y
SY
Sun
Chengwen
C
D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage; D017704:Baroreflex / Q000187:drug effects; D001640:Bicuculline / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D018755:GABA Agonists / Q000008:administration & dosage; D018756:GABA Antagonists / Q000008:administration & dosage; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D015918:Infusion Pumps, Implantable; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000008:administration & dosage; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation
D018755:GABA Agonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D000804:Angiotensin II; D009118:Muscimol; C066430:CGP 35348; D001418:Baclofen; D019331:NG-Nitroarginine Methyl Ester; D001640:Bicuculline