Effects Of Angiotensin-(1-7)on Cardiac Electrophysiology In Isolated Myocytes Of Guinea Pig

OBJECTiVE It is well recognized that the renin-angiotensin system has an important role in cardiovascular physiology, fluid homeostasis, and cell function. Angiotensin (Ang) II has long been considered the main biologically active product of an endocrine system that contributes significantly to the pathogenesis of arterial hypeitension, renal dysfunction, and congestive heart failure. However, newer studies have shown that Angiotensin-(1-7) may oppose to the pressor and proliferative action of Ang II. Treatment with ACEI or AT1 receptor antagomsts may increase the plasma level of Ang-(1-7). Until now, the mechanisms underlying the beneficial effects of Ang-(l-7) on hearts have not been fully established. Therefore, the purpose of the present study was to clariI~ the effects of Ang-(l-7) on the cardiac eletrophysiology in guinea pig myocytes. We have also made comparisons with AngH.METHODS Single myocytes were obtained from guinea pig hearts by an enzymatic dissociation procedure. Membrane currents were recorded with patch electrodes in a whole-cell clamp configuration. The first data were usually taken after the amplitude of currents had been stabilized. After that, we investigated the effects of Ang-(1-7) and Angfl on L-type calcium currents (I~), delayed rectifiering K~ currents (IK)~ inward rectifiering K~ currents (IK1) and sodium currents (慛a)?Moreover, we observed the effects of specific AT1 antagonist Valsartan and non specific AT antagonist Sarthran on ion channels with the present of AngIv7(1-7) or Angll. In another group, papillary muscles were dissected quickly from guinea pig hearts in normal Tyrode抯 solution at room temperature and mounted in a constant temperature apparatus at 370C. Preparations were stimulated at 0.5Hz, 1Hz and 2Hz alier 30 minutes. A further 30 minutes equilibration was observed before collection of data was begun. The rest potential (RP), action potential aniplitude (APA), maximal depolerization rate (Vmax) and action potential duration (APD) were recorded following administration of Ang-(1-7) or AngJI.RESULTS The present results showed that: (1) Ang-(1-7) 0.5 j.imol.L? lJ.Lmol.L?and 2~tmol.L?increased the amplitude of 1~-L from-9.64 ?1.19(pA/pF) to -10.23 ?2.16, -11.45 ?2.78 and -12.76 + l.76(pAIpF). Angll lmnolIL, lOnmolJL and S0nniol/L increased the amplitude of 1C~L from -8.87?.18(pAIpF) to -9.34? 96 -11.23 ?.56 and -12.45? .82(pA/pF), respectively. The current-voltage relationships of 慍a-L showed that it had no effect on activating potential, peak potential and reverse potential. The effects of Ang-(1-7) or Angll on 慍~L can be eliminated by specific AT1 antagonist Valsartan and non-specific AT antagonist Sarthran.Therefore, the effects of Ang-(1-7) on L~L was the same as the effects of Angll. However, Ang-(1-7) increased the amplitude of 1C~L at the jimol.L?level, Angll at the nmol.L?level.(2) Ang-(1-7) also increased the amplitude of 慘 in a dose dependent manner. Ang-(1-7) 0.5 jimol.L? ljimol.L?and 2j~mol.L ?increased the amplitude of 慘 from13.53 ?0.92(pA/pF) to 15.67 ?1.74, 16.96 ?2.15 and 17.58 ?2.73(pAIpF). On the contrary, Angll lnmol.L? lOnmol.L?and S0nmol.L 慸ecreased the amplitude of 慘 from 13.94?l.49(pAIpF) to 13.04?.17, 11.12?.37 and 10.86?.48(pA/pF). The current-voltage relationships of 慘 showed that Ang-(1-7) and Angll had no effect on activating potential and peak potential. The effects of Ang-(1-7) or AngII on 慘 could be almost completely eliminated by Valsarthan. Sarthran could eliminateVthe effects of Ang-(1-7), but Valsartan could not. Therefore, Ang-(l-7) increased the amplitude of 慘 through non specific AT1 receptor. Angll decreased the amplitude of 慘 through specific AT1 receptor. (3) Ang-(1-7)1桰 O0~imol.L?had no effect on the amplitude of 慛a and 慘l (P>0.05). AngIL lnmol.L?lOnmol.L?and SOnmol.L7?increased the amplitude of 慘I from -38.67?.24(鐍AIpF) to -43.06?.23, -47.98?.31 and -53.47?7.84 (pAIpF) . It had no effect on the outward cu...