Journal of molecular and cellular cardiology
-
J. Mol. Cell. Cardiol. · May 1997
Beta-adrenergic receptor signalling in stunned myocardium of conscious pigs.
The primary goal of this study was to compare the effects of isoproterenol which stimulates beta-adrenergic receptors and forskolin, and NKH 477, a water soluble derivative of forskolin, which stimulate adenylyl cyclase in stunned myocardium of conscious pigs, previously instrumented for measurements of left ventricular pressure and dP/dt, arterial pressure, and wall thickening. Ten min of coronary artery occlusion induced transmural reductions in blood flow (radioactive microspheres) in subepicardium (-98 +/- 2%) and subendocardium (-99 +/- 1%). Wall thickening (piezoelectric crystals) fell from 2.50 +/- 0.26 mm to -0.26 +/- 0.26 mm and remained depressed at 1.37 +/- 0.19 mm after 20-30 min coronary artery reperfusion, reflecting myocardial stunning. ⋯ Basal and forskolin-stimulated adenylyl cyclase activities were decreased slightly, but significantly, in the stunned subendocardium but not in the subepicardium, while isoproterenol stimulation of adenylyl cyclase activity showed no differences. In summary, paradoxical responses to beta-adrenergic receptor stimulation were observed in stunned myocardium, with pharmacological stimulation with isoproterenol evoking enhanced responses, and neural stimulation with inferior vena caval occlusion eliciting depressed responses. The diminished responses to forskolin in vivo, in stunned myocardium were out of proportion to the biochemical measurements, and may be attributed to neurally mediated cardiac effects of forskolin, since the responses to direct stimulation of adenylyl cyclase by NKH 477 were preserved.
-
J. Mol. Cell. Cardiol. · May 1997
Norepinephrine pretreatment attenuates Ca2+ overloading in rat trabeculae during subsequent metabolic inhibition: improved contractile recovery via an alpha 1-adrenergic, PKC-dependent signaling mechanism.
The present study was designed in order to investigate more precisely the role of calcium homeostasis maintenance in protein kinase C (PKC) mediated preconditioning. We used a 15 min pre-incubation period, with 1 mumol/l exogenous norepinephrine (NE) to pharmacologically precondition isolated, superfused rat trabeculae against contractile dysfunctioning following 120 min of metabolic inhibition (MI, in 2 mmol/l CN- containing Tyrode without glucose at 1 Hz stimulation frequency). Contractile recovery was studied during a subsequent 60 min recovery period (RP, in glucose containing Tyrode at 0.2 Hz). ⋯ Also in this case [Ca2+]i in the failing group NE-IV trabeculae after 40 min of MI was increased substantially, compared to the value measured in the recovering preparations (4.75 +/- 1.00 and 0.60 +/- 0.08 mumol/ l, respectively). The relative importance of both alpha-adrenergic and beta-adrenergic receptor pathways in this preconditioning-like effect of NE-pretreatment, was investigated using specific blockers. The results point to an alpha 1-adrenergic receptor mediated signaling mechanism, which enhances PKC-dependent control of [Ca2+]i from the onset of rigor development during MI.