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This Article Full Text Full Text (PDF) All Versions of this Article: 289/3/E412    most recent 00049.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by McConville, P. Articles by Lakatta, E. G. Search for Related Content PubMed PubMed Citation Articles by McConville, P. Articles by Lakatta, E. G.

Temporal dynamics of inotropic, chronotropic, and metabolic responses during ₁- and ₂-AR stimulation in the isolated, perfused rat heart

¹Nuclear Magnetic Resonance Unit, Laboratory of Clinical Investigation and ²Laboratory for Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland

Submitted 2 February 2004 ; accepted in final form 24 March 2005

During the -adrenergic receptor (-AR)-mediated stress response in the heart, the relations between functional responses and metabolism are ill defined, with the distinction between ₁- and ₂-AR subtypes creating further complexity. Specific outstanding questions include the temporal relation between inotropic and chronotropic responses and their metabolic correlates. We sought to elucidate the relative magnitudes and temporal dynamics of the response to ₁- and ₂-AR stimulation and the energy expenditure and bioenergetic state related to these responses in the isolated perfused rat heart. Inotropic [left ventricular developed pressure (LVDP) and dP/dt], chronotropic [heart rate (HR)], and metabolic responses were measured during ₁- (n = 9; agonist: norepinephrine) and ₂- (n = 9; agonist: zinterol) AR stimulation. Myocardial oxygen consumption (MO₂) was measured using fiber-optic oximetry, and high-energy phosphate levels and intracellular pH were measured using ³¹P NMR spectroscopy. A multiple-dose protocol was used, with near-maximal -AR stimulation at the highest doses. In both ₁ and ₂ groups, there were dose-dependent increases in LVDP, dP/dt, HR, and MO₂. The inotropic response showed more rapid onset, washout, and variation during dose than did the chronotropic response and was closely correlated with MO₂. This suggests that the myocardial bioenergetic state is more closely related to the inotropic response than to the chronotropic response. In addition, ₁-AR stimulation resulted in a greater magnitude and rate of onset of inotropic and MO₂ responses than did ₂-AR stimulation during maximal stimulation. However, a similar decrease in intracellular energy charge was seen in the two groups, consistent with a greater rate of oxidative phosphorylation during ₁- than during ₂-AR stimulation.

receptors; adrenergic; metabolism; myocardial oxygen consumption; inotropy; chronotropy; phosphorus-31 nuclear magnetic resonance; rat heart; adrenergic receptor

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