Enhanced release of endothelium-derived hyperpolarizing factor in small coronary arteries from rats with congestive heart failure.
1. Previous studies have suggested that the production of nitric oxide (NO) is reduced in coronary vessels of animals with congestive heart failure (CHF). However, the response to endothelium-derived hyperpolarizing factor (EDHF) in small coronary resistance arteries from CHF rats has not been investigated. The aim of the present study was to determine whether flow-induced dilation (FID) is altered in small coronary arteries from CHF rats and to characterize the role of EDHF in this process. 2. Small coronary arteries (97 +/- 6 microm) were isolated from control rats and from rats in which CHF was induced by left coronary artery ligation. The arteries were cannulated at 60 mmHg with flow. Changes in internal diameter were examined using videomicroscopy. 3. There was no significant difference in FID in small coronary arteries between control and CHF rats (68 +/- 6 vs 61 +/- 4% (expressed as a percentage of maximal dilation induced by nitroprusside (%MaxD(NP))), respectively). Flow-induced dilation in control rat vessels showed greater attenuation by N(G)-monomethyl-L-arginine (L-NMMA) than vessels from CHF rats (%NO-mediated FID 32 +/- 5 vs 16 +/- 3% (%MaxD(NP)), respectively). Pretreatment with indomethacin had no significant effect on FID in vessels from either rat group. Flow-induced dilation was attenuated by KCl (40 mmol/L) to a greater degree in vessels from CHF rats in the presence of L-NMMA and indomethacin compared with vessels from control rats (%EDHF-mediated FID: 36 +/- 4 vs 25 +/- 5% (%MaxD(NP)), respectively). Flow-induced dilation was abolished by removal of the endothelium and was significantly decreased in vessels from CHF rats in response to charybdotoxin plus apamin or tetrabutylammonium compared with control rat vessels. 17-Octadecynoic acid had no significant effect on FID in vessels from either control or CHF rats. 4. In conclusion, the FID of small coronary arteries is mediated by K+ channels, including the K(Ca) channels. Endothelium-derived hyperpolarizing factor-mediated dilation may compensate for the loss of NO-mediated dilation in CHF.
Ueda
Atsunori
A
Department of Internal Medicine, Division of Coronary Heart Disease, Hyogo College of Medicine, Nishinomiya, Japan.
Ohyanagi
Mitsumasa
M
Koida
Satsuki
S
Iwasaki
Tadaaki
T
D000818:Animals; D001685:Biological Factors / Q000378:metabolism / Q000502:physiology*; D002317:Cardiovascular Agents / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; D002317:Cardiovascular Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide