Fig 6. Roles of nitric oxide (NO), endothelium-derived hyperpolarizing factors (EDHF), and calcium-activated K⁺ (K_Ca) channels in renal arcuate arteries.

Acetylcholine (ACh) can induce endothelium-dependent vasodilation by the release of NO (①) and EDHF (②) from endothelial cells in renal arcuate arteries. NO is derived from endothelial NO synthase (eNOS), while prostacyclin (PGI₂) and epoxyeicosatrienoic acids (EETs, as EDHFs) are generated from arachidonic acids by cyclooxygenase (COX), and cytochrome P-450 (CYP) epoxygenase, respectively. EETs facilitate the hyperpolarization of smooth muscle cells and vascular relaxation through K⁺ efflux mediated by the opening of K_Ca channels either in endothelial cells or in smooth muscle cells. The K⁺ released from K_Ca channels of endothelial cells into the subendothelial space (potential connective tissue space beneath the endothelium) subsequently actives inward rectifying K⁺ (K_ir) channels on smooth muscle cells, while producing K⁺ efflux as well. In the present study, the contribution of NO and EDHF to endothelium vasodilation was impaired and the activity of K_Ca channels was downregulated in renal arcuate arteries of obese Zucker (OZ) rats at 20 weeks of age, but PGI₂ had no effect on ACh-elicited vasodilation. Barium chloride, inhibitor of the K_ir channel; Charybdotoxin (Cha)+Apamin, inhibitor of the K_Ca channel; Glibenclamide, inhibitor of the K_ATP channel; Indomethacin, inhibitor of COX; L-NNA, inhibitor of eNOS; NS1619, agonist of the K_Ca channel; and PPOH or 17-ODYA, inhibitors of CYP epoxygenase.