Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen.
Endogenous angiotensin (ANG) II and ANG-(1-7) act at the nucleus tractus solitarius (NTS) to differentially modulate neural control of the circulation. The role of these peptides endogenous to NTS on cardiovascular reflex function was investigated in transgenic rats with low brain angiotensinogen (Aogen) due to glial overexpression of an antisense to Aogen (ASrAOGEN) and in Sprague-Dawley (SD) rats. Arterial baroreceptor reflex sensitivity (BRS) for control of heart rate (HR) in response to increases in mean arterial pressure (MAP) was tested before and after bilateral microinjection of the angiotensin type 1 (AT(1)) receptor blocker candesartan or the ANG-(1-7) receptor blocker (d-Ala(7))-ANG-(1-7) into the NTS of urethane-chloralose-anesthetized ASrAOGEN and SD rats. Baseline MAP was higher in ASrAOGEN than in SD rats under anesthesia (P < 0.01). Injection of candesartan or (d-Ala(7))-ANG-(1-7) decreased MAP (P < 0.01) and HR (P < 0.05) in ASrAOGEN, but not SD, rats. The BRS at baseline was similar in ASrAOGEN and SD rats. Candesartan increased BRS by 41% in SD rats (P < 0.01) but was without effect in ASrAOGEN rats. In contrast, the reduction in BRS after (d-Ala(7))-ANG-(1-7) administration was comparable in SD (31%) and ASrAOGEN rats (34%). These findings indicate that the absence of glia-derived Aogen is associated with 1) an increase in MAP under anesthesia mediated via AT(1) and ANG-(1-7) receptors within the NTS, 2) the absence of an endogenous ANG II contribution to tonic inhibition of BRS, and 3) a continued contribution of endogenous ANG-(1-7) to tonic enhancement of BRS.
Sakima
Atsushi
A
Hypertension & Vascular Disease Center, Wake Forest Univ School of Medicine, Winston-Salem, NC 27157-1032, USA.
Averill
David B
DB
Kasper
Sherry O
SO
Jackson
Larhonda
L
Ganten
Detlev
D
Ferrario
Carlos M
CM
Gallagher
Patricia E
PE
Diz
Debra I
DI
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000502:physiology*; D008297:Male; D009457:Neuroglia / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D013777:Tetrazoles; D000808:Angiotensinogen; C081643:candesartan