Role of PKC in the late phase of microvascular protection induced by preconditioning.
BACKGROUND
We hypothesized that the late phase of microvascular protection induced by ischemic preconditioning or by adenosine is protein kinase C (PKC) dependent.


METHODS
The cremaster muscle of male Sprague-Dawley rats underwent 45 min of ischemic preconditioning and, 24 h later, 4 h of warm ischemia followed by 60 min of reperfusion. To mimic the effects of IPC, adenosine (ADO; an adenosine receptor agonist) or 4-phorbol 12-myristate 13-acetate (PMA; a PKC activator) was delivered to the vascular network of the cremaster 24 h before the prolonged ischemia via local intra-arterial infusion. To block the microvascular protection induced by ADO or IPC, chelerythrine (CHE; a PKC blocker) was given by local intra-arterial infusion prior to the administration of ADO or the initiation of IPC. Microvascular responses in the cremaster muscle to ischemic preconditioning or pharmacological preconditioning were determined by measuring terminal arteriole diameter and capillary perfusion using intravital microscopy and by the evaluation of the endothelium-dependent nitric oxide system in terminal arterioles.


RESULTS
Blockade of PKC using CHE on day 1 eliminated both ADO- and IPC-induced microvascular protections seen on day 2. However, the microvascular protection induced by the administration of PMA (without IPC) that was given 24 h before the 4 h of warm ischemia/reperfusion was significantly better than the control group response (sham IPC), but was not as good as the protection induced by IPC or ADO alone.


CONCLUSIONS
The overall results from these studies suggest that ischemic or ADO preconditioning induces late-phase microvascular protection in skeletal muscle by a PKC-dependent mechanism.
Division of Plastic Surgery, Department of Surgery, University of Nevada School of Medicine, Las Vegas, NV 89102, USA.
Wei Z
WZ
Wang
Linda L
LL
Stepheson
Gary L
GL
Anderson
Frederick N
FN
Miller
Kayvan T
KT
Khiabani
Willarm A
WA
Zamboni
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000201:enzymology; D002196:Capillaries / Q000201:enzymology; D002273:Carcinogens / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000201:enzymology; D019194:Ischemic Preconditioning; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D009569:Nitric Oxide; D011493:Protein Kinase C; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate