title: Effects of carbenoxolone on flow-mediated vasodilatation in healthy adults.
abstract: Gap junctions play a key role in maintaining the functional integrity of the vascular wall. Using carbenoxolone (CBX) as a gap junction blocker, we aimed to assess the contribution of gap junctions in the vascular wall to flow-mediated vasodilatation (FMD) in healthy adults. Percentage FMD (%FMD) and circulating vasoactive molecules/activity, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), aldosterone, cortisol, plasma renin activity (PRA), and endothelin (ET-1), were measured in 25 healthy volunteers (mean age: 30.1 ± 5.4 yr; 14 males) before and after oral administration of CBX (100 mg). %FMD decreased after ingestion of CBX (9.71 ± 3.1 vs. 3.40 ± 2.0%; P < 0.0001). The levels of ANP, BNP, cortisol, and ET-1 remained stationary, while both PRA and aldosterone decreased (P < 0.005) after CBX ingestion. Blood pressure and heart rate were minimally changed by CBX. Inhibition of gap junctional communication by CBX impairs FMD in healthy persons, suggesting that physiologically, vascular gap junctions participate in the maintenance of FMD. CBX does not induce the release of vasoconstricting molecules or enhance vasoconstriction, suggesting that inhibition of gap junctional communication by CBX underlies the impairment of FMD. Therefore, administering CBX in FMD examination can be a way to follow the effect of gap junctions on endothelial function, but further work remains to verify the specificity of CBX effect.
authors.affiliation: Cardiovascular Section, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Lan
authors.forename: Charles Jia-Yin
authors.initials: CJ
authors.lastname: Hou
authors.forename: Chih-Hsuan
authors.initials: CH
authors.lastname: Yen
authors.forename: Bing-Fu
authors.initials: BF
authors.lastname: Shih
authors.forename: An-Mei
authors.initials: AM
authors.lastname: Wang
authors.forename: Tzung-Yi
authors.initials: TY
authors.lastname: Lee
authors.forename: Cheng-Ho
authors.initials: CH
authors.lastname: Tsai
authors.forename: Hung-I
authors.initials: HI
authors.lastname: Yeh
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000450:Aldosterone / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002229:Carbenoxolone / Q000008:administration & dosage / Q000494:pharmacology*; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006940:Hyperemia / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D013997:Time Factors; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin; D002229:Carbenoxolone; D006854:Hydrocortisone