Role of BK channels in testosterone-induced relaxation of the aorta in spontaneously hypertensive rats.
The previous data indicated that the testosterone (Tes)-induced relaxation of thoracic aorta is greater in spontaneously hypertensive rats (SHR) than in normotensive rats (Wistar-Kyoto rats; WKY) and that there were differences between SHR and WKY in the functions of K(ATP), K(v), and K(Ca) channels. The present study was carried out to ascertain the mechanisms of the Tes-induced relaxation. Indomethacin (30 muM) pretreatment suppressed the Tes-induced relaxation. Following noradrenalin (NA)-induced vasoconstriction, the relaxation induced by Tes was significantly attenuated by endothelium removal in SHR (not in WKY), but the dilatory effect of Tes following KCl-induced vasoconstriction was not attenuated by endothelium removal. After tetraethylammonium (K(Ca) channel inhibitor) or iberiotoxin (large conductance, Ca(2+) activated BK channel inhibitor) pretreatment, the Tes-induced relaxation was attenuated in SHR, but not in WKY. This attenuation in SHR was not observed after endothelium removal. The above results suggest that the relaxation induced by Tes following NA-induced vasoconstriction in SHR results from hyperpolarization due to BK channel opening.
Unemoto
Tamao
T
Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Matsushita
Mayumi
M
Tamura
Kazuhiro
K
Tanaka
Yoshio
Y
Koike
Katsuo
K
Kogo
Hiroshi
H
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013739:Testosterone / Q000494:pharmacology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D013757:Tetraethylammonium Compounds; D014662:Vasoconstrictor Agents; D013739:Testosterone; D011189:Potassium Chloride; C064719:iberiotoxin; D009638:Norepinephrine