SUMMARY 1. It is reported that α 1 ‐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 α 1 ‐receptors and adenosine A1‐receptors contribute to the mechanism of PC. Therefore, we investigated the extent of the contribution of α 1 ‐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, α 1 ‐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 α 1 ‐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 α 1 ‐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.
In rabbits and rats, both stimulation of α1-adrenoceptors and ischemic preconditioning (PC) reduce infarct size. Activation of α1b-adrenoceptors play an important role in the PC effect on ventricular function in rats. However, the α1-adrenoceptors have not been reported to be related to the PC effect in rabbits, because the infarct size-reducing effect of PC is not blocked by the nonselective α-adrenoceptor antagonist, phenoxybenzamine (POB) or by the α1-adrenoceptor antagonist, BE2254. However, we speculated that α1b-adrenoceptors but not α1a-adrenoceptors may be related to the infarct size-reducing effect of PC in rabbit hearts. Thus we examined in rabbits whether the α1b-adrenoceptor blocker chloroethyl-clonidine (CEC), the α1a-adrenoceptor blocker 5-methylurapidil (5-MU), the selective α1-adrenoceptor antagonist bunazosin (BN), and the nonselective α-adrenoceptor antagonist phenoxybenzamine (POB) can block the PC effect on infarct size. Eighty-eight anesthetized open-chest Japanese white male rabbits were subjected to 30-min coronary occlusion and 48-h reperfusion. In five PC groups, the rabbits were subjected to a single 5-min occlusion and 5-min reperfusion before 30-min sustained ischemia. In the PC groups, those with CEC (3 mg/kg, n = 10), 5-MU (3 mg/kg, n = 10), BN (0.3 mg/kg, n = 10), POB (4 mg/kg, n = 10), or placebo saline (n = 10) were pretreated before PC. In the non-PC groups, those with CEC (3 mg/kg, n = 7), 5-MU (3 mg/kg, n = 7), BN (0.3 mg/kg, n = 7), POB (4 mg/kg, n = 7), or placebo saline (n = 10) were pretreated before 30-min sustained ischemia. After a 48-h reperfusion, the infarct size was measured histologically and expressed as a percentage of the area at risk. PC caused a marked reduction of infarct size as compared with the non-PC control (10 ± 3% vs. 42 ± 2%; p < 0.05). The PC effect was completely blocked by CEC (36 ± 2%) and by BN (42 ± 4%) but not by 5-MU (14 ± 1%) or POB (13 ± 2%). None of the drugs by itself affected the infarct size. Stimulation of α1b-adrenoceptors but not of α1a-adrenoceptors during PC plays an important role in the PC effect on infarct size. This may explain the previous confusion concerning the PC blocking effect of various α1-blockers.
The effects of exposure to extremely low frequency electric fields (ELF EFs) on plasma lipid peroxide levels and antioxidant activity (AOA) in Sprague-Dawley rats were studied. The test was based on comparisons among rats treated with a combination of the oxidizing agent, 2,2'-azobis(2-aminopropane) dihydrochloride (AAPH) and 50 Hz EF of 17.5 kV/m intensity for 15 min per day for 7 days, AAPH alone, EF alone or no treatment. EF significantly decreased the plasma peroxide level in rats treated with AAPH, similar to treatment by ascorbic acid or the superoxide dismutase. Ascorbic acid increased AOA; however, EF and superoxide dismutase did not change AOA compared with sham exposure in stressed rats. No influence on the lipid peroxide level and AOA in unstressed rats was observed with EF exposure alone. Although the administration of AAPH decreased AOA, this decrease did not change when EF was added. These data indicate that the ELF EF used in this study influenced the lipid peroxide level in an oxidatively stressed rat.
Introduction: Most patients with dialysis have left ventricular (LV) hypertrophy and fibrosis which may result in heart failure. Although estimation of LV function and fluid status is helpful in tr...
