Key result
ACh-induced EDHF-mediated relaxation in superior mesenteric arteries was weaker in spontaneously hypertensive rats than in Wistar Kyoto rats, utilizing BKCa components in addition to SKCa/IKCa.
EDHF-mediated relaxations in superior mesenteric arteries are impaired in spontaneously hypertensive rats and utilize BKCa components due to altered subunit ratios.
Impaired EDHF relaxation in hypertensive arteries leaves open BKCa targeting; human studies needed before any clinical consideration.
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 Ca 2+ -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 Ca 2+ -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.
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Ando et al. (2018) studied Hypertension. Spontaneously hypertensive rats (SHR) vs. Wistar Kyoto rats (WKY) was evaluated on Endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh). ACh-induced EDHF-mediated relaxation in superior mesenteric arteries was weaker in spontaneously hypertensive rats than in Wistar Kyoto rats, utilizing BKCa components in addition to SKCa/IKCa.
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