Eicosanoids and membrane properties in arteries of aged spontaneously hypertensive rats.
OBJECTIVE
The arteries of aged spontaneously hypertensive rats (SHR) exhibit spontaneous electrical activity together with membrane depolarization. Vascular eicosanoid production is increased in SHR, which is further accelerated with aging. We tested the hypothesis that eicosanoids are involved in spontaneous electrical activity, membrane depolarization or both in mesenteric arteries of aged SHR.


METHODS
Membrane potentials were recorded with microelectrodes from the mesenteric arteries of aged (24 months and older) SHR, aged Wistar-Kyoto (WKY) rats and adult (6- to 8-month-old) SHR.


RESULTS
The membrane potential was less negative in aged SHR (-38.5 +/- 0.9 mV) than in either aged WKY rats or adult SHR (-49.8 +/- 0.5 and -47.2 +/- 0.6 mV, respectively; P < 0.05 for both). Spontaneous electrical activity (5-20 mV, 1-7/min) was present only in arteries of aged SHR. Spontaneous electrical activity was not affected by phentolamine, atropine or tetrodotoxin, but was abolished by indomethacin, a cyclooxygenase inhibitor, and ONO-3708, a thromboxane A2/prostaglandin H2 receptor antagonist. Furthermore, indomethacin and ONO-3708 hyperpolarized the membrane by about 5 mV in aged SHR but not in the other two groups. Spontaneous electrical activity was enhanced by a thromboxane A2 analog and prostaglandin H2, and was abolished by a Ca2+ antagonist, nicardipine, and Ca(2+)-free solution.


CONCLUSIONS
These findings suggest that cyclooxygenase-dependent eicosanoids contribute importantly to both spontaneous electrical activity and membrane depolarization, presumably through activation of the thromboxane A2/prostaglandin H2 receptor, in mesenteric arteries of aged SHR, and that spontaneous electrical activity is mediated by a Ca2+ influx through voltage-dependent Ca2+ channels.
Fujii
K
K
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. fujii@intmed2.med.kyushu.u-ac.jp
Onaka
U
U
Abe
I
I
Fujishima
M
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008839:Microelectrodes; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013779:Tetrodotoxin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology
D015220:Calcium Channels; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D010975:Platelet Aggregation Inhibitors; D013779:Tetrodotoxin; D013928:Thromboxane A2; D001285:Atropine; C049855:ONO 3708; D007213:Indomethacin; D010646:Phentolamine