Reduced effects of endothelium-derived hyperpolarizing factor in ocular ciliary arteries from spontaneous hypertensive rats

Vascular peripheral resistance is increased during hypertension, and endothelium-derived hyperpolarizing factor (EDHF) is an important for regulating vasodilation in small arteries. Therefore we characterized the role of EDHF in regulating vascular resistance of ocular ciliary arteries from spontaneous hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Isometric tension recordings were used in isolated ocular ciliary artery segments from SHR and WKY. Ocular ciliary arteries pre-contracted with 100 μM norepinephrine exhibited a concentration-dependent relaxation to acetylcholine, and the effect on SHR arteries was smaller than that on WKY arteries (P < 0.05). The EDHF-mediated component of this relaxation, determined in the presence of 100 μM l-NAME plus 10 μM indomethacin, was also smaller in SHR than in WKY arteries (P < 0.05). Apamin (1 μM), a blocker of small-conductance calcium-activated K+ (KCa) channels, had no effect on EDHF-mediated relaxation in either preparation. However, charybdotoxin (0.1 μM), which blocks intermediate- and large-conductance KCa channels, and iberiotoxin (0.1 μM), which blocks large-conductance KCa channels, almost completely suppressed EDHF-mediated relaxation in both preparations. The tension of ciliary arteries from both SHR and WKY was increased above baseline by 100 μM l-NAME plus 10 μM indomethacin. In these preparations, apamin had no effect on the tension in arteries from either SHR or WKY. However, both charybdotoxin and iberiotoxin further increased tension above that induced by l-NAME and indomethacin. The increase was smaller for SHR than WKY (P < 0.05). In summary, the ability of EDHF to relax ocular ciliary artery vascular tone in SHR is smaller than in WKY. The large-conductance calcium-activated K+ channel is utilized in EDHF-signaling pathway.