Impairment of Calcium-Activated Potassium Channels in Endothelium-Derived Hyperpolarizing Factor Responses in Spontaneously Hypertensive Rats

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To examine the effect of chronic hypertension on endothelium-derived hyperpolarizing factor（ EDHF）responses, the hearts of Wistar-Kyoto rats（ WKY） and spontaneously hypertensive rats（ SHR） were isolated andperfused using Langendorff system with constant perfusion pressure. Bradykinin increased coronary fl ow（ CF） dosedependentlyand this was not aff ected by NG-nitro-L-arginine methyl ester or indomethacin, indicating that bradykinin’seff ect on CF was not mediated by nitric oxide or prostacyclin but by EDHF. Bradykinin-induced CF increase was smallerin SHR than in WKY. Tetrabutylammonium（ a non-specific KCa channel blocker） abolished bradykinin-induced CFincrease in both rats. 1-Ethyl-2-benzimedazolinone（ 1-EBIO, an agonist of intermediate conductance KCa channel）-inducedincrease in CF was smaller in SHR than in WKY. 1,3-Dihydro-1-[2-hydroxy-5（- trifl uoromethyl） phenyl]-5（- trifl uoromethyl）-2H-benzimidazol-2-one（ NS1619, an agonist of large conductance KCa channel）-induced increase in CF did not differbetween SHR and WKY. In early stage of hypertension, there was no signifi cant diff erence between SHR and WKY inbradykinin- and 1-EBIO-induced increases in CF. In conclusion, EDHF response in coronary microcirculation is impairedin SHR due to dysfunction of intermediate-conductance calcium-activated potassium channels.