| Objectives:1. To investigate the myogenic effects of extracellular acidification (EA) on the resting tone of isolated rat coronary arteriole (RCA) rings.2. To explore the possible involvement of voltage-dependent potassium channel (Ky), ATP-sensitive potassium channel (KATP), and large conductance calcium-activated potassium channel (BKCa) in EA-induced myogenic responses of isolated RCA rings.3. To explore the possible involvement of p38Mitogen-activated protein kinase (p38MAPK) in EA-induced myogenic responses of isolated RCA rings.Methods:1. Male rats (200-250g) were killed by decapitation and the heart was quickly removed and placed into4℃physiological salt solution (PSS) immediately. Coronary arteries were separated under integrated microscope and cuted into2mm-long rings, and then they were fixed on the wire myograph. The changing of isolated RCA rings’ tension were recorded by PowerLab and DMT systems.2. Kv inhibitor4-Aminopyridine (4-AP)(0.3mmol/L,1mmol/L), KATP inhibitor Glibenclamide (Gli)(0.003mmol/L,0.01mmol/L,0.03mmol/L) and BKca inhibitor Tetraethylammonium (TEA)(1mmol/L,3mmol/L) in EA-induced myogenic responses of isolated RCA rings were observed.3. The inhibitor of p38MAPK SB239063(1μmol/L) in EA-induced myogenic responses of isolated RCA rings was observed.Results:1. With the extracellular pH decreased (pH7.2,7.0,6.8,6.6), the resting tone of isolated RCA rings increased. The maximum contraction induced by KC1(60mmol/L) was considered as100%, and the contraction percentages of pH7.2,7.0,6.8,6.6were (4.51±1.48)%,(38.84±7.24)%,(78.61±4.10)%,(101.79±3.64)%.2. The contraction percentages of pH7.2,7.0,6.8,6.6were (6.57±2.35)%,(34.42±9.48)%,(76.41±8.58)%,(101.91±3.02)%;4-AP (0.3mmol/L) obviously inhibited the contraction of isolated RCA rings induced by pH6.6(P<0.05), and the contraction percentages was (85.85± 6.61)%;4-AP (1mmol/L) significantly inhibited the contraction of isolated RCA rings induced by pH7.0,6.8,6.6(P<0.05), and the contraction percentages were (15.39±9.68)%,(42.07±12.81)%,(55.76±15.66)%. Compared with4-AP (0.3mmol/L),4-AP (1mmol/L) significantly inhibited the contraction of isolated RCA rings induced by pH6.6(P<0.05).3. The contraction percentages of pH7.2,7.0,6.8,6.6were (6.09±3.20)%,(37.97±11.10)%,(75.73±7.85)%,(102.83±3.64)%; Gli (0.003mmol/L) obviously increased the contraction of isolated RCA rings induced by pH6.8,6.6(P<0.05), and the contraction percentages were (110.12±11.81)%,(124.24±10.14)%; Gli (0.01mmol/L) obviously inhibited the contraction of isolated RCA rings induced by pH6.8,6.6(P<0.05), and the contraction percentages were (56.19±3.98)%,(59.08±5.52)%; Gli (0.03mmol/L) significantly inhibited the contraction of isolated RCA rings induced by pH6.8,6.6(P<0.05), and the contraction percentages were (46.19±8.64)%,(29.73±6.12)%. Compared with Gli (0.01mmol/L), Gli (0.03mmol/L) significantly inhibited the contraction of isolated RCA rings induced by pH6.6(P<0.05).4. The contraction percentages of pH7.2,7.0,6.8,6.6were (8.91±5.57)%,(32.83±7.19)%,(74.01±7.28)%,(102.76±3.94)%; TEA (1mmol/L) obviously increased the contraction of isolated RCA rings induced by pH7.0,6.8,6.6(P<0.05), and the contraction percentages were (56.94±14.46)%,(103.22±10.27)%,(119.63±6.55)%; TEA (3mmol/L) significantly increased the contraction of isolated RCA rings induced by pH7.0,6.8,6.6(P<0.05), and the contraction percentages were (64.97±11.79)%,(119.32±17.81)%,(134.77±18.20)%. The contraction of isolated RCA rings induced by pH6.6between TEA (1mmol/L) and TEA (3mmol/L) had no significantly difference (P>0.05).5. The contraction percentages of pH7.2,7.0,6.8,6.6were (7.85±3.27)%,(39.04±5.19)%,(78.28±5.39)%,(103.89±3.42)%; SB239063(1μmol/L) significantly inhibited the contraction of isolated RCA rings induced by pH7.0,6.8,6.6(P<0.05), and the contraction percentages were (19.77±4.47)%,(49.21±6.15)%,(62.55±4.63)%.Conclusions:1. Extracellular acidification contracts RCA.2. Manipulation of Kv, KATP and BKCa may be involved in EA-induced contraction in RCA.3. Activation of p38MAPK may be involved in EA-induced contraction in RCA. |
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