The initiating factors of late preconditioning in skeletal muscle.
OBJECTIVE
The goal of these studies was to determine the initiating factors for late preconditioning in the microcirculation of skeletal muscle.


METHODS
The cremaster muscle of male Sprague-Dawley rats underwent 4 h of ischemia and then 60 min of reperfusion. Ischemic preconditioning (IPC) consisted of 45 min of ischemia but was done 24 h before the 4 h of ischemia. To mimic the effects of IPC in the late phase, adenosine (ADO) or sodium nitroprusside (SNP) was given 24 h before the prolonged ischemia via local intraarterial infusion. To block the effects of IPC in the late phase, 8-sulfophenyl-theophylline (a nonspecific ADO receptor blocker) or N(W)-nitro-l-arginine (a nonselective nitric oxide synthase antagonist) was given prior to IPC. Microvascular response to IPC and pharmacological preconditioning were determined by measuring arteriole diameters and capillary perfusion using intravital microscopy.


RESULTS
Administration of ADO or SNP on day 1 without IPC produced a similar microvascular protection against prolonged ischemia/reperfusion on day 2 as that induced by IPC alone. In contrast, blocking ADO receptors or nitric oxide synthase on day 1 just prior to IPC eliminated the IPC-induced microvascular protection seen on day 2. In addition, inhibition of nitric oxide synthase on day 1 diminished the protection induced by ADO, but blocking ADO receptors on day 1 did not compromise the protection induced by SNP.


CONCLUSIONS
The results from these studies suggest that up regulation of ADO is the initiating factor with secondary up regulation of nitric oxide in late preconditioning. Both ADO and nitric oxide contribute to initiating microvascular protection in the late phase of IPC.
Wang
W Z
WZ
Department of Surgery, University of Nevada School Medicine, Las Vegas, Nevada 89102, USA.
Guo
S Z
SZ
Anderson
G L
GL
Miller
F N
FN
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019194:Ischemic Preconditioning; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D014665:Vasodilator Agents; D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D000241:Adenosine