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Reduced hyperpolarization of endothelial cells following high dietary Na + : effects of enalapril and tempol
Author(s) -
Bondarenko Alexander,
Panasiuk Olga,
Stepanenko Lubov,
Goswami Nandu,
Sagach Vadim
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2012.05718.x
Subject(s) - hyperpolarization (physics) , apamin , endocrinology , medicine , chemistry , enalapril , membrane potential , endothelium , potassium channel , angiotensin converting enzyme , biochemistry , stereochemistry , blood pressure , nuclear magnetic resonance spectroscopy
Summary High dietary Na + is associated with impaired vascular endothelial function. However, the underlying mechanisms are not completely understood. In the present study, we investigated whether the endothelial hyperpolarization response to acetylcholine ( AC h) exhibited any abnormalities in Wistar rats fed a high‐salt diet ( HSD ) for 1 month and, if so, whether chronic treatment with the angiotensin‐converting enzyme inhibitor enalapril or the anti‐oxidant tempol could normalize the response. Membrane potential was recorded using the perforated patch‐clamp technique on the endothelium of rat aorta. Acetylcholine (2 μmol/L) produced a hyperpolarization sensitive to TRAM ‐34, a blocker of intermediate‐conductance Ca 2+ ‐sensitive K + channels ( IK Ca ), but not to apamin, a blocker of small‐conductance Ca 2+ ‐sensitive K + channels ( SK Ca ). NS 309 (3 μmol/L), an activator of SK Ca and IK Ca channels, produced a hyperpolarization of similar magnitude as AC h. In the HSD group, the AC h‐evoked hyperpolarization was significantly attenuated compared with that in the control group, which was fed normal chow rather than an HSD . Similarly, the hyperpolarization produced by NS 309 was weaker in tissues from HSD ‐fed rats. Combination of HSD with chronic enalapril treatment (20 mg/kg per day for 1 month) normalized endothelial hyperpolarizing responses to AC h. Chronic tempol treatment (1 mmol/L in tap water for 1 month) prevented the reduced hyperpolarization to AC h. The results of the present study indicate that excess in dietary Na + results in a failure of endothelial cells to generate normal IK C a channel‐mediated hyperpolarizing responses. Our observations implicate oxidative stress mediated by increased angiotensin II signalling as a mechanism underlying altered endothelial hyperpolarization during dietary salt loading.