EDHF, NO and a prostanoid: hyperpolarization‐dependent and ‐independent relaxation in guinea‐pig arteries
- 1 June 2000
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 130 (3), 605-618
- https://doi.org/10.1038/sj.bjp.0703332
Abstract
The contribution of endothelium-derived hyperpolarizing factor (EDHF), nitric oxide (NO) and a prostanoid (PG) to endothelium-dependent hyperpolarization and relaxation were assessed in coronary and mammary arteries of guinea-pigs by integration of the responses evoked during discrete applications of acetylcholine (ACh). The results of this integration approach were compared with those using traditional peak analysis methods. N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) and indomethacin (1 microM), alone or in combination, were without effect on peak hyperpolarizations or relaxations while they markedly reduced the integrated responses in both arteries. Integrated responses attributed to NO and PG were larger than those attributed to EDHF in the coronary artery (at 2 microM ACh, hyperpolarization (mV s): NO, 4200+/-91; PG, 5046+/-157; EDHF, 1532+/-94; relaxation (mN s mm(-1)): NO, 2488+/-122; PG, 2234+/-96; EDHF, 802+/-54). Integrated responses attributed to NO, PG and EDHF were similar in the mammary artery (at 2 microM ACh, hyperpolarization: NO, 347+/-69; PG, 217+/-49; EDHF, 310+/-63; relaxation: NO, 462+/-94; PG, 456+/-144; EDHF, 458+/-40). Gilbenclamide (1 microM) all but abolished the hyperpolarization attributable to NO and PG but not EDHF in both arteries allowing assessment of the role of the hyperpolarization in relaxation. Gilbenclamide was without effect on the integrated relaxation due to NO but significantly reduced the relaxation associated with PG in the two arteries. In conclusion, integration of the responses enabled a more complete assessment of the contribution of EDHF, NO and PG to endothelium-dependent responses, which were strikingly different in the two arteries. There is commonality in the role of hyperpolarization in relaxation in both arteries: EDHF-dependent relaxation is strongly dependent on hyperpolarization; hyperpolarization plays an important role in PG relaxation, whereas it has a small facilitatory role in NO-dependent relaxation.Keywords
This publication has 45 references indexed in Scilit:
- REGULATION OF VASCULAR TONE BY ENDOTHELIUM-DERIVED HYPERPOLARIZING FACTORClinical and Experimental Pharmacology and Physiology, 1999
- Inhibition of endothelium‐dependent hyperpolarization by endothelial prostanoids in guinea‐pig coronary arteryBritish Journal of Pharmacology, 1999
- Endothelium-dependent hyperpolarization in resting and depolarized mammary and coronary arteries of guinea-pigsBritish Journal of Pharmacology, 1999
- Interactions between endothelium‐derived relaxing factors in the rat hepatic artery: focus on regulation of EDHFBritish Journal of Pharmacology, 1998
- Roles of calcium‐activated and voltage‐gated delayed rectifier potassium channels in endothelium‐dependent vasorelaxation of the rabbit middle cerebral arteryBritish Journal of Pharmacology, 1998
- Characterization and modulation of EDHF-mediated relaxations in the rat isolated superior mesenteric arterial bedBritish Journal of Pharmacology, 1997
- The Importance of the Hyperpolarizing Mechanism Increases as the Vessel Size Decreases in Endothelium-Dependent Relaxations in Rat Mesenteric CirculationJournal of Cardiovascular Pharmacology, 1996
- Regional differences in endothelium‐dependent relaxation in the rat: contribution of nitric oxide and nitric oxide‐independent mechanismsActa Physiologica Scandinavica, 1995
- The endothelium mediates a nitric oxide-independent hyperpolarization and relaxation in the rat hepatic arteryActa Physiologica Scandinavica, 1994