The Effects Of PH Change On The Myogentic Reactivity Of Small Arterial Rings In Different Organs

Objective:To investigate the effects and possible mechanism(s) of different pH on isolated rat small arteries(coronary arteries, renal arteries, cerebral arteries, mesenteric arteries).Methods:We suspend the isolated small arteries of rat in organ chambers for isometric tension, which was recorded with Powerlab and DMT system. Whether the gradient changes of pH can influent the contractile state of small arteries is observed. The inhibitors of eNOS (L-NAME,1×10-4mol/L), Na+/Ca2+exchanger (KB-R7943,1×10-6mol/L), Chloride channel (NPPB,3×10-5mol/L), calcium channel(verapamil,1×10-5mol/L), Na+/H+exchanger (amiloride,3×10-5mol/L),inner and outer Ca2+were all used to study the effects of pH6.4on contractility of the coronary artery. Additionally, we also study the effects of inotropic agents and the relaxation responses of SNP or Pina to KCl or U-46619or PE preconstricted rings in different pH values.Result:①The decreasing of extracellular pH can enhance vascular resting tone of isolated rat coronary arteries. The resting tone is steady at the point of pH7.4, pH7.2, pH7.0. The maximum contractile percentage of pH6.8, pH6.6, pH6.4are (40.51±10.71)%,(56.32±9.44)%,(100.09±17.46)%respectively. The resting tone of renal arteries, cerebral arteries, mesenteric arteries do not change with pH value.②Both inner and outer Ca2+involve contractile state of coronary arteries in pH6.4. Calcium channel inhibitor verapamil partly inhibit pH6.4-induced contraction. Compared with the control group, KB-R7943, ouabain had no significant effects on pH6.4-induced contraction, there was no statistical significance(P>0.05). NPPB, amiloride could significantly inhibit pH6.4-induced contraction(P<0.05), whereas the L-NAME can enhance pH6.4-induced contraction(P<0.05).③The contraction effect of inotropic agents on the small arteries are different with pH changed. Compared with the pH7.4group in coronary artery, the contraction effect of U-46619and KCl in low pH group increased significantly(P<0.05), when the pH reached7.4,7.2,7.0the Emax of U-46619are (5.65±1.08)mN,(8.87±0.89)mN,(10.71±1.14)mN respectively and the Emax of KC1are (6.08±0.70)mN,(7.10±0.93)mN, (8.80±1.20)mN respectively; For cerebral arteries, the contraction effect of U-46619dicreased when the pH came down(P<0.05), whereas the contraction effect of KCl are nearly changeless(P>0.05)when the pH reached7.4,7.2,7.0,6.8,6.6, the Emax of U-46619are (9.68±0.83)mN,(8.40±0.89)mN,(5.89±0.65)mN,(4.23±0.82)mN,(2.02±0.79)mN respectively and the Emax of KCl are (6.27±0.44)mN,(6.08±0.44)mN,(5.82±0.27)mN,(5.67±0.26)mN,(5.36±0.16)mN. For renal arteries, the contraction effect of KCl are not changed significantly(P>0.05)and the contraction effect of PE decreased at the point of pH6.8and pH6.6(P<0.05), when the pH reached7.4,7.2,7.0,6.8,6.6, the Emax of KCl are (4.61±0.45)mN,(4.58±0.19)mN,(4.37±0.19)mN,(4.34±0.38)mN,(4.25±0.40)mN and when the pH reached6.8,6.6, the Emax of PE are (7.82±0.81)mN,(6.99±0.83)mN.④of different pH groups, Sodium nitroprusside (SNP) and pinacidil (Pina) can relaxe the rat small arteries preconstricted by U-46619(10-6mol/L) or PE(10-6mol/L) or KCl(60mmol/L) in a dose-dependent manner. But the relaxation effect is variety.Conclusion:When acidosis occurs, the decreasing pH alter the myogentic reactivity of small arterial rings. Overall,the decreasing pH can enhance resting tone of isolated rat coronary arteries and have no influence on the renal arteries, cerebral arteries and mesenteric arteries. The possible mechanisms of pH6.4-induced contraction in coronary rings were associated with inner and outer Ca2+, chloride channel, Na+/H+exchanger. The effects of inotropic agents and the relaxation responses of SNP or Pina to KCl or U-46619on preconstricted rings in different pH values are variety for different kind of arteries.