title: Reduced hyperpolarization of endothelial cells following high dietary Na+: effects of enalapril and tempol.
abstract: 1. 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 (ACh) 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. 2. 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)). NS309 (3 μmol/L), an activator of SK(Ca) and IK(Ca) channels, produced a hyperpolarization of similar magnitude as ACh. 3. In the HSD group, the ACh-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 NS309 was weaker in tissues from HSD-fed rats. 4. Combination of HSD with chronic enalapril treatment (20 mg/kg per day for 1 month) normalized endothelial hyperpolarizing responses to ACh. Chronic tempol treatment (1 mmol/L in tap water for 1 month) prevented the reduced hyperpolarization to ACh. 5. The results of the present study indicate that excess in dietary Na(+) results in a failure of endothelial cells to generate normal IK(Ca) 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.
authors.affiliation: Circulatory Physiology Department, AA Bogomoletz Institute of Physiology, Kiev, Ukraine. abond01@biph.kiev.ua
authors.forename: Alexander
authors.initials: A
authors.lastname: Bondarenko
authors.forename: Olga
authors.initials: O
authors.lastname: Panasiuk
authors.forename: Lubov
authors.initials: L
authors.lastname: Stepanenko
authors.forename: Nandu
authors.initials: N
authors.lastname: Goswami
authors.forename: Vadim
authors.initials: V
authors.lastname: Sagach
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001030:Apamin / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D010091:Oximes / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013113:Spin Labels
chemical_list: C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D018679:Cholinergic Agonists; D003497:Cyclic N-Oxides; D007211:Indoles; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D010091:Oximes; D011720:Pyrazoles; D051640:Small-Conductance Calcium-Activated Potassium Channels; D012982:Sodium, Dietary; D013113:Spin Labels; C411671:TRAM 34; D001030:Apamin; D004656:Enalapril; D000109:Acetylcholine; C001803:tempol