Differential participation of calcium-activated potassium channel in endothelium-dependent hyperpolarization-type relaxation in superior mesenteric arteries of spontaneously hypertensive rats

The purpose of this study was to determine the relationship of K_Ca channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca²⁺-activated K⁺ channels (SK_Ca and IK_Ca) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs. WKY). Treatment with large-conductance Ca²⁺-activated K⁺ channels (BK_Ca) inhibitor specifically attenuated relaxation in SHR, but not in WKY. Protein expression of IK_Ca and SK_Ca in the arteries did not differ between the 2 groups, whereas ratio of sloβ1 subunit to α subunit of BK_Ca was increased in SHR (vs. WKY). These results suggest that EDHF-mediated relaxations in superior mesenteric arteries are impaired in SHR, and utilize components of BK_Ca in addition to SK_Ca/IK_Ca channel activities, that the increased participation of BK_Ca may be attributable to alterations in α and sloβ1 subunit ratio, and that components unrelated to K_Ca activity may also contribute to the difference between SHR and WKY arteries.