Facilitative interactions between noradrenergic and purinergic signaling during preconditioning of the rat heart.
Recent developments in cardiac physiology have focused on the mechanisms underlying preconditioning against ischemia-reperfusion injury. Sensing, transduction and cardioadaptation to the initial stimulus suggests species-specific differences in strategy. We and others have found that ischemic stress can trigger catecholamine (alpha1-adrenoreceptor)-dependent mechanisms of preconditioning. However, in rabbits and dogs, adenosine receptor mechanisms appear to predominate. In contrast, the role of the adenosine receptors in rat remains controversial. Anticipating a minor role for this metabolite, we examined its ability to induce protection in rat heart against a modest ischemic injury and also its relationship to the noradrenergic alpha1 pathway. Although redundant pathways for inducing adaptation to stress are possible, single transient ischemic stress surprisingly utilizes both alpha1-adrenoreceptors and adenosine P1 receptors in obligate roles. Thus blockade of either purinergic P1 or alpha1-adrenergic receptors abolished functional protection induced by single transient ischemic stimulus. Selective noradrenergic alpha1-adrenoreceptor stimulation was sufficient to protect cardiac recovery after modest ischemic injury, and was unaffected by purinergic blockades, suggesting that this is the primary stress adaptation pathway for rat. However, exogenous purinergic P1 stimulated protection was abolished in either reserpine pretreated, or alpha1-adrenoreceptor blockaded hearts. Therefore the cardioadaptive ischemic preconditioning mechanisms in rat may involve facilitative modulation of a primary pathway rather than redundancy.
Winter
C B
CB
Department of Surgery, University of Colorado Health Sciences Center, Denver, USA.
Cleveland
J C
JC
Butler
K L
KL
Bensard
D B
DB
Mitchell
M B
MB
Harken
A H
AH
Banerjee
A
A
D000222:Adaptation, Physiological; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D018340:Receptors, Adrenergic, alpha-1; D018047:Receptors, Purinergic P1; D009638:Norepinephrine