Ca²⁺-activated K⁺-channels (KCa), in particular the small- and intermediate (SKCa and IKCa) 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 SKCa and IKCa channels in ACh-induced relaxations is reduced, due to decreased expression of SKCa and IKCa channel proteins in rat small mesenteric arteries. Nitric oxide- and prostacyclin-independent vasorelaxation to ACh was similar in small mesenteric arteries (MA) of sham-operated (untreated, SHAM) and Ang II-14d rats. Catalase had no inhibitory effects on these relaxations. The highly selective SKCa channel blocker UCL 1684 almost 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 rats. Expression levels of both mRNA and protein SK3 were significantly reduced in MA of Ang II-14d. The IKCa 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, whereas protein levels of IK1 were not, but tended to be lower in MA of AngII-14d. 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.