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Endothelium‐derived hyperpolarizing factor and potassium use different mechanisms to induce relaxation of human subcutaneous resistance arteries

2001; Wiley; Volume: 133; Issue: 6 Linguagem: Inglês

10.1038/sj.bjp.0704143

1476-5381

C. A. McIntyre, C. H. Buckley, Gregory C. Jones, Thekkepat C. Sandeep, Robert Andrews, Andrew I. ELLIOTT, Gillian A. Gray, Brent C. Williams, John McKnight, Brian R. Walker, P. W. F. Hadoke,

Heart Rate Variability and Autonomic Control

This investigation examined the hypothesis that release of K + accounts for EDHF activity by comparing relaxant responses produced by ACh and KCl in human subcutaneous resistance arteries. Resistance arteries (internal diameter 244±12 μm, n =48) from human subcutaneous fat biopsies were suspended in a wire myograph. Cumulative concentration‐response curves were obtained for ACh (10 −9 – 3×10 −5 M ) and KCl (2.5 – 25 m M ) following contraction with noradrenaline (NA; 0.1 – 3 μ M ). ACh (E max 99.07±9.61%; −LogIC 50 7.03±0.22; n =9) and KCl (E max 74.14±5.61%; −LogIC 50 2.12±0.07; n =10)‐induced relaxations were attenuated ( P <0.0001) by removal of the endothelium (E max 8.21±5.39% and 11.56±8.49%, respectively; n =6 – 7). Indomethacin (10 μ M ) did not alter ACh‐induced relaxation whereas L ‐NOARG (100 μ M ) reduced this response (E max 61.7±3.4%, P <0.0001; n =6). The combination of ChTx (50 n M ) and apamin (30 n M ) attenuated the L ‐NOARG‐insensitive component of ACh‐induced relaxation (E max : 15.2±10.5%, P <0.002, n =6) although these arteries retained the ability to relax in response to 100 μ M SIN‐1 (E max 127.6±13.0%, n =3). Exposure to BaCl 2 (30 μ M ) and Ouabain (1 m M ) did not attenuate the L ‐NOARG resistant component of ACh‐mediated relaxation (E max , 76.09±8.92, P =0.16; n =5). KCl‐mediated relaxation was unaffected by L ‐NOARG+indomethacin (E max ; 68.1±5.6%, P =0.33; n =5) or the combination of L ‐NOARG/indomethacin/ChTx/apamin (E max ; 86.61±14.02%, P =0.35; n =6). In contrast, the combination of L ‐NOARG, indomethacin, ouabain and BaCl 2 abolished this response (E max , 5.67±2.59%, P <0.0001, n =6). The characteristics of KCl‐mediated relaxation differed from those of the nitric oxide/prostaglandin‐independent component of the response to ACh, and were endothelium‐dependent, indicating that K + does not act as an EDHF in human subcutaneous resistance arteries. British Journal of Pharmacology (2001) 133 , 902–908; doi: 10.1038/sj.bjp.0704143