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Basic Research in Cardiology

, Volume 92, Issue 6, pp 391–401 | Cite as

The negative functional and metabolic effects of muscarinic stimulation are enchanced byβ-adrenergic activation in control and hypertrophic dog hearts in vivo

  • P. M. Scholz
  • P. Rabindranauth
  • K. L. Naim
  • H. R. Weiss
  • J. Tse
Original contribution
  • 30 Downloads

Abstract

The aim of the current study was to determine if the effects of muscarinic stimulation on left ventricular function and metabolism are greater during β-adrenergic activation, whether a cyclic GMP-mediated mechanism is responsible, and if this is altered by left ventricular hypertrophy (LVH) induced by aortic valve stenosis. Acetylcholine (Ach) (5 μg/kg/min) and/or isoproterenol (Iso) (0.1 μg/kg/min) was infused into a branch of the left anterior descending (LAD) artery in 8 control and 8 LVH open-chest anesthetized dogs. LVH increased heart weight, heart-to-body weight ratio and systolic left ventricular pressure. LVH reduced muscarinic receptor density (fmol/mg protein) (control: 149.2±18.6; LVH: 77.8±8.6), but not affinity. Alone, Ach had no effect on regional force, work or metabolism. Iso increased peak force (g) (control: baseline-7.4±0.4; Iso-12.4±2.2; LVH: baseline-6.7±0.8; Iso-16.3±2.7, regional work (g mm/min)) (control: baseline-1250±186; Iso-1813±409; LVH: baseline-927±235; Iso-1244±222), and O2 consumption (ml O2/min/100 g) (control: baseline-3.3±0.2; Iso-8.1±2.0; LVH: baseline-4.8±1.0; Iso-8.3±1.1). During Iso, Ach reduced segment shortening (control: Iso-14.5±1.2; Iso+Ach-10.5±1.8; LVH: Iso-10.4±1.5; Iso+Ach-7.6±1.3) and peak force (control: Iso+Ach-7.7±1.0; LVH: Iso+Ach-10.5±1.4). Ach also reduced work (control: Iso+Ach-875±217; LVH: Iso+Ach-776±180) and O2 consumption (control: Iso+Ach-3.4±0.7; LVH: Iso+Ach-3.6±0.6) in the presence of Iso. Cyclic GMP was higher in the LVH animals during all treatments and was elevated from baseline by Ach in both groups. Neither Iso nor Iso+Ach had a significant effect on cyclic GMP. Thus, the negative functional and metabolic effects of muscarinic stimulation are enhanced during β-adrenergic activation. This does not, however, appear to be dependent on a cyclic GMP-mediated mechanism. Despite reduced number of muscarinic receptors, this response was not altered by pressure-induced cardiac hypertrophy.

Key words

Cardiac hypertrophy acetylcholine dog β-adrenergic stimulation myocardial O2 consumption regional myocardial function 

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Copyright information

© Steinkopff Verlag 1997

Authors and Affiliations

  • P. M. Scholz
    • 1
  • P. Rabindranauth
    • 1
  • K. L. Naim
    • 2
  • H. R. Weiss
    • 2
  • J. Tse
    • 3
  1. 1.Department of SurgeryUMDNJ-Robert Wood Johnson Medical SchoolNew BrunswickUSA
  2. 2.Departments of Physiology & BiophysicsUMDNJ-Robert Wood Johnson Medical SchoolPiscatawayUSA
  3. 3.Department of AnesthesiaUMDNJ-Robert Wood Johnson Medical SchoolPiscatawayUSA

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