Beta-adrenergic receptor downregulation and recovery in heart and lung in the Fischer 344 rat: effects of aging and correlation with mRNA levels.
Using indirect methods to downregulate beta-adrenergic receptor (BAR) density, several investigators have observed an aging-related delay in the recovery of BAR density after downregulation and suggested this finding may in part explain the decreased beta-adrenergic responsiveness associated with aging. We downregulated BAR density in male Fischer 344 rats ages 3, 12, and 24 months using the direct BAR agonist, metaproterenol. Lung and heart BAR density and BAR mRNA levels were measured daily for 5 days during recovery. Heart BAR density was downregulated significantly more in the 24-month compared to the 3-month-old animals (ANOVA p < .05). The rate of recovery of heart BAR density was greater in the 24-month compared to the 3-month-old animals (ANOVA, p = .05). Lung BAR density showed no significant age-related differences at baseline, after downregulation, or during recovery. There was no significant change in lung or heart BAR mRNA levels observed in association with downregulation of BAR density. The previously documented decrease in myocardial beta-adrenergic responsiveness with aging in this animal appears to not be related to delayed or incomplete recovery of BAR density after agonist-induced downregulation, but may be associated with greater initial downregulation of heart BAR density.
Raitt
M H
MH
Division of Cardiology, University of Washington, Seattle, USA.
Tamblyn
C
C
Allen
J M
JM
Abrass
I B
IB
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation; D006321:Heart / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009921:Metaproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D009921:Metaproterenol