Ca²⁺-activated K⁺-channels (K_Ca), in particular the small- and intermediate (SK_Ca and IK_Ca) channels are key players in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in small arteries. Hypertension is characterized by an endothelial dysfunction possibly via reduced EDHF release and/or function. We hypothesize that during angiotensin II(14-days)-induced hypertension (Ang II-14d), the contribution of SK_Ca and IK_Ca channels in ACh-induced relaxations is reduced, due to decreased expression of SK_Ca and IK_Ca channel proteins in small rat mesenteric arteries. Nitric oxide (NO) and prostacyclin-indpendent vasorelaxation to ACh was similar in small mesenteric arteries (MA) of sham-operated (SHAM) and Ang II-14d rats. Catalase had no inhibitory effects on these relaxations. The highly selective SK_Ca channel blocker UCL 1684 completely blocked these responses in MA of SHAM, but partially in MA of Ang II-14d rats. These changes were pressure-dependent since UCL 1684 caused a greater inhibition in MA of 1-day Ang II-treated normotensive rats compared to Ang II-14d. Expression levels of both mRNA and protein SK3 was significantly reduced in MA of Ang II-14d rats. The IK_Ca channel blocker TRAM-34 resulted in comparable reductions in the relaxation responses to ACh in MA of SHAM and Ang II-14d. Relative mRNA expression levels of IK1 were significantly reduced in MA of Ang II-14d rats, whereas protein levels of IK1 were not, but tended to be lower in MA of Ang II-14d rats. The findings demonstrate that EDHF-like responses are not compromised in a situation of reduced functional activity and expression of SK3 channels in small mesenteric arteries of Ang II-induced hypertensive rats. The role of IK1 channels is less clear, but might compensate for reduced SK3 activity.