Impaired heart rate baroreflex in older rats: role of endogenous angiotensin-(1-7) at the nucleus tractus solitarii.
Age-related baroreflex reductions in function may originate from central neural dysregulation as well as vascular structural/functional changes. We determined the role of 2 angiotensin (Ang) peptides at the nucleus tractus solitarii in age-related baroreflex impairment. Baroreflex sensitivity control of heart rate in response to increases in blood pressure was tested in younger (3 to 5 months) and older (16 to 20 months) anesthetized male Sprague-Dawley rats before and after bilateral solitary tract injections of the Ang II type 1 (AT1) receptor antagonist candesartan (24 pmol) or the Ang-(1-7) antagonist (D-Ala7)-Ang-(1-7) (144 fmol or 24 pmol). Basal reflex sensitivity of older rats was significantly lower than younger rats. In younger rats, the reflex was facilitated by bilateral candesartan injections and attenuated by bilateral (D-Ala7)-Ang-(1-7) injections. In older rats, the reflex was facilitated by AT1 blockade; however, (D-Ala7)-Ang-(1-7) injected into the solitary tract nucleus had no effect. Neprilysin mRNA in the medulla was lower in older rats compared with younger rats, whereas angiotensin-converting enzyme (ACE), ACE2, and mas receptor mRNA levels of older rats did not differ from values of younger rats. Thus, opposing actions of endogenous Ang II and Ang-(1-7) in the solitary tract nucleus contribute to baroreflex function in response to increases in mean arterial pressure of younger rats. The attenuated counterbalancing effect of Ang-(1-7) on baroreflex function is lost in older rats, which may be attributable to diminished production of the peptide from neprilysin.
Sakima
Atsushi
A
The Hypertension and Vascular Disease Center, Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032, USA.
Averill
David B
DB
Gallagher
Patricia E
PE
Kasper
Sherry O
SO
Tommasi
Ellen N
EN
Ferrario
Carlos M
CM
Diz
Debra I
DI
D000375:Aging / Q000502:physiology*; D000803:Angiotensin I / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D001713:Biphenyl Compounds; D006339:Heart Rate / Q000502:physiology*; D007267:Injections; D008297:Male; D015260:Neprilysin / Q000235:genetics; D010446:Peptide Fragments / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010446:Peptide Fragments; D012333:RNA, Messenger; D013777:Tetrazoles; D000803:Angiotensin I; D015260:Neprilysin; C118790:angiotensin I (1-7); C081643:candesartan