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 and perfused using Langendorff system with constant perfusion pressure. Bradykinin increased coronary flow (CF) dose-dependently and this was not affected by N
G-nitro-L-arginine methyl ester or indomethacin, indicating that bradykinin's effect on CF was not mediated by nitric oxide or prostacyclin but by EDHF. Bradykinin-induced CF increase was smaller in SHR than in WKY. Tetrabutylammonium (a non-specific K
Ca channel blocker) abolished bradykinin-induced CF increase in both rats. 1-Ethyl-2-benzimedazolinone (1-EBIO, an agonist of intermediate conductance K
Ca channel)-induced increase in CF was smaller in SHR than in WKY. 1,3-Dihydro-1-[2-hydroxy-5-(trifluoromethyl) phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS1619, an agonist of large conductance K
Ca channel)-induced increase in CF did not differ between SHR and WKY. In early stage of hypertension, there was no significant difference between SHR and WKY in bradykinin- and 1-EBIO-induced increases in CF. In conclusion, EDHF response in coronary microcirculation is impaired in SHR due to dysfunction of intermediate-conductance calcium-activated potassium channels.
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