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 microM 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 microM l-NAME plus 10 microM indomethacin, was also smaller in SHR than in WKY arteries (P < 0.05). Apamin (1 microM), a blocker of small-conductance calcium-activated K(+) (K(Ca)) channels, had no effect on EDHF-mediated relaxation in either preparation. However, charybdotoxin (0.1 microM), which blocks intermediate- and large-conductance K(Ca) channels, and iberiotoxin (0.1 microM), which blocks large-conductance K(Ca) 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 microM l-NAME plus 10 microM 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.
Dong
Yaru
Y
Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
Watabe
Hiroshi
H
Cui
Jizhe
J
Abe
Sanae
S
Sato
Noriko
N
Ishikawa
Hitoshi
H
Yoshitomi
Takeshi
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D001794:Blood Pressure; D019842:Ciliary Arteries / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D006339:Heart Rate; D006973:Hypertension / Q000503:physiopathology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D001685:Biological Factors; D024681:Potassium Channels, Calcium-Activated; C067410:endothelium-dependent hyperpolarization factor; D000109:Acetylcholine; D009638:Norepinephrine