ISSN:
1435-1803
Schlagwort(e):
Cardiac hypertrophy
;
acetylcholine
;
dog
;
β-adrenergic stimulation
;
myocardial O2 consumption
;
regional myocardial function
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
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.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00796213
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