Altered contractile and ion channel function in rabbit portal vein with dietary atherosclerosis.
This study was performed to determine the effects of dietary atherosclerosis on the pharmacology and ion channel properties of rabbit portal vein (PV). New Zealand White rabbits were fed normal rabbit chow +/- 2% cholesterol for 10 wk. Contractions to norepinephrine (NE) and serotonin were studied under isometric conditions with longitudinal strips. Ca2+ and K+ currents (ICa and IK, respectively) were recorded in freshly dispersed myocytes by whole cell voltage clamp methods. Cholesterol feeding increased total plasma cholesterol levels from 28.4 +/- 5.2 to 1,387 +/- 172 mg/dl as well as the cholesterol-to-phospholipid molar ratio of the PV from 0.34 +/- 0.02 to 0.66 +/- 0.08. Only maximum contractile responses to serotonin were larger in atherosclerotic PV when normalized to the maximum KCl response. Concentration-active stress curves of the atherosclerotic PV to NE and serotonin were shifted to the left. Maximum values of ICa were larger in myocytes from atherosclerotic compared with control animals (4.4 +/- 0.4 vs. 3.1 +/- 0.2 pA/pF, P < 0.05). The voltage dependence of activation and availability of ICa was shifted toward more negative potentials by approximately 10 mV. Whole cell K+ currents were smaller in atherosclerotic myocytes. At a test voltage of +20 mV, IK averaged 14.9 +/- 2.8 pA/pF in control compared with 7.7 +/- 0.8 pA/pF in atherosclerotic myocytes from a holding potential of -80 mV with external Ca2+ concentration of 5 mM. The reversal potential for IK tail currents was significantly less negative in atherosclerotic myocytes (-70 +/- 1 vs. -64 +/- 1 mV).(ABSTRACT TRUNCATED AT 250 WORDS)
Cox
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Bockus Research Institute, Graduate Hospital, Philadelphia, PA 19146, USA.
Tulenko
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TN
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002791:Cholesterol, Dietary; D004036:Diet, Atherogenic; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012016:Reference Values; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D015220:Calcium Channels; D002791:Cholesterol, Dietary; D007473:Ion Channels; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D012701:Serotonin; D009638:Norepinephrine