Study On The Mechanisms And Effects Of KB-R7943 On Isolated Aorta And Arteriole Rings Of Rats

Objective:To investigate the effects and the possible mechanism(s) of KB-R7943 on isolated aorta and arteriole rings pre-contracted by vasoactive agents from adult rats.Methods:Isolated aorta and arterial rings (renal artery, cerebral artery, coronary artery and aorta) of rat were suspended in organ chambers for isometric tension recording with Powerlab and DMT system. The relaxation responses of KB-R7943 to KCl preconstricted rings were recorded and its comparison with that of sodium nitroprusside (SNP) was also recorded. The inhibitors of eNOS(N-nitro-L-arginine methyl ester,10-4 mol/L), cyclooxygenase(Indometacin,10-5 mol/L), specific K+ channels were used to study on the relaxation effect of KB-R7943. Norepinephrine(NE), Phenylephrine(PE),5-hydroxytryptamine(5-HT), U-46619 and inner and outer Ca2+ were used as contractors to observe if the constriction was affected by KB-R7943 which was pre-incubated in advance.Result:KB-R7943(10-8～10-6 mol/L) had no significant effect on resting tone of the isolated aorta and arteriole, and there was no statistical significance (P<0.05) compared with control group. KB-R7943 and SNP had a dose-dependent relaxation on aorta and arteriole ring which was constricted by KCl (60mmol/L).The inhibitor of NOS (L-NAME 10-4 mol/L) could make a inhibition of relaxation effect induced by KB-R7943, whereas the inhibition of cyclooxygenase (Indomethacin 10-5 mol/L) had no such effect. The inhibitor of Kca channel (TEA 10-2 mol/L) and KV channel (4-AP 10-3 mol/L L) could significantly inhibit the relaxation effect which was induced by KB-R7943, however the inhibitor of KATP channel (Gli 10-5 mol/L) and KIR channel (BaCl2 10-4 mol/L) had no such significant effect. KB-R7943 (10-6mol/L～10-5mol/L) showed a dose-dependent inhibition constriction of renal artery induced by PE,5-HT, U-46619, and made them the dose-effect curve non-parallel right shifted. In the calcium-less PSS (complexed by EGTA), after KB-R7943 with different concentration (10-6,3×10-6 and 10-5 mol/L) was preincubated respectively, NE (10-6 mol/L) could make a rapid and transient constriction and CaCl2 (2.5mmol/L) was added subsequently; Compared with the controlled group, high-concentration of KB-R7943 (10-6 mol/L) could significantly reduce the constriction effect induced by NE and CaCl2(P<0.01), whereas low-concentration of KB-R7943 (10-6 and 3×10-6 mol/L) had no such significant effect.Conclusion:①KB-R7943 could produce a dose-dependent relaxation of aorta and arteriole constriction of rats induced by KCl;②The relaxation effect of KB-R7943 might have a relationship with ion channel of KCa, KV and the endothelium synthesis and release of NO;③KB-R7943 could produce a vascular relaxation effect on renal artery induced by kinds of constrictor, and there were no selectivity;④High concentration of KB-R7943 had a certain inhibition effect of the constriction induced by calcium influx and intracellular calcium release.