Alpha1-receptor or adenosine A1-receptor dependent pathway alone is not sufficient but summation of these pathways is required to achieve an ischaemic preconditioning effect in rabbits.
1. It is reported that alpha1-receptors and adenosine A1-receptors are involved in the ischaemic preconditioning (PC) effect on infarct size (IS). However, it is still unclear to what extent alpha1-receptors and adenosine A1-receptors contribute to the mechanism of PC. Therefore, we investigated the extent of the contribution of alpha1-receptors and adenosine A1 receptors to the PC effect on IS and examined the relationship between these receptors and protein kinase C. 2. Infarct size was measured in rabbits subjected to 30 min ischaemia and 48 h reperfusion. Tyramine (Tyr) was intravenously administered before 30 min ischaemia in the absence or presence of bunazosin (BN, alpha1-receptor blocker) and staurosporine (ST), a protein kinase C inhibitor, respectively. R(-)N6-(2-phenylisapropyl)-adenosine (PIA), a selective adenosine A1 agonist, was intravenously administered before 30 min ischaemia in the absence or presence of 8-p-sulphophenyltheophylline (8SPT), an adenosine blocker and ST, respectively. In the PC groups, BN, BN + PIA, 8SPT, 8SPT + Tyr or placebo saline was injected before or during PC. 3. Both Tyr and PIA reduced the IS, which was blocked by BN and 8SPT, respectively. The IS-reducing effect of Tyr or PIA was blocked by ST. The IS-reducing effect of PC was completely blocked by BN and 8SPT, respectively. The blocking effect of BN on the IS-reducing effect of PC was abolished by adding PIA during PC ischaemia. The blocking effect of 8SPT on the IS-reducing effect of PC was abolished by adding Tyr before PC ischaemia. 4. These data suggest that an alpha1-receptor dependent pathway exists and an adenosine A1-receptor dependent pathway, stimulation of both of which activates protein kinase C, then reduces the IS. However, exclusive stimulation of a single alpha1-receptor dependent pathway or a single adenosine A1-receptor dependent pathway alone is not sufficient but the summation of these pathways is required to achieve a PC effect on IS in rabbits.
Baba
Kaori
K
Second Department of Internal Medicine, Gifu University School of Medicine, Tsukasa-machi, Gifu, Japan.
Minatoguchi
Shinya
S
Zhang
Chengxi
C
Kariya
Tatsuya
T
Uno
Yoshihiro
Y
Kawai
Takao
T
Takahashi
Masahiko
M
Takemura
Genzou
G
Fujiwara
Hisayoshi
H
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology; D011817:Rabbits; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D011799:Quinazolines; D043682:Receptor, Adenosine A1; D018340:Receptors, Adrenergic, alpha-1; D014665:Vasodilator Agents; C047235:N-(1-methyl-2-phenylethyl)adenosine; C031433:8-(4-sulfophenyl)theophylline; C018176:bunazosin; D013806:Theophylline; D011493:Protein Kinase C; D019311:Staurosporine; D000241:Adenosine; D014439:Tyramine