Endothelins: vasoconstrictor effects and localization in canine cerebral arteries.
1. The vascular effects of endothelin and localization of endothelin-like immunoreactivity were characterized in isolated cerebral arteries of dogs. 2. Endothelin-like immunoreactivity was detected in a few populations of endothelial cells of dog basilar artery. 3. Endothelin-1, endothelin-2 and endothelin-3 contracted isolated ring preparations of cerebral arteries in a dose-dependent manner independently of the presence of endothelium. The ED50 values (and 95% confidence intervals) for the contraction were 411 pM (242-697 pM) and 478 pM (295-776 pM) for endothelin-1 and endothelin-2, respectively. Endothelin-3 induced vascular contraction at a higher concentration (ED50 = 26.5 nM, 95% confidence interval = 15.7-45.7 nM). 4. The increases in tone induced by endothelin-1 and endothelin-2 did not return to the resting level after repeated washings, while a rinse with Krebs solution reversed the vasoconstrictor response to endothelin-3. The endothelins did not cause any vasodilator response in arteries precontracted with uridine 5'-triphosphate even in the presence of intact endothelial cells. 5. NiCl2 (1 mM) attenuated the contractions induced by endothelin-3 (10-300 nM) and those to relatively low doses (1 nM) but not higher doses (10-100 nM) of endothelin-1 and endothelin-2. The contractions in response to endothelin-1, endothelin-2 and endothelin-3 were greatly attenuated in Ca(2+)-free solutions although high concentrations of endothelin-1 and endothelin-2 still evoked contractions. 6. These results suggest that the vasoconstriction induced by endothelin-3 and lower doses of endothelin-1 and endothelin-2, largely depends on the influx of Ca2+ ions. The apparent insensitivity to Ni2+ shows that additional distinct mechanisms also operate in the vasconstrictor responses to high concentrations of endothelin-1 and endothelin-2. 7. The presence of endothelin-like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen.
Saito
A
A
Department of Pharmacology, University of Tsukuba, Japan.
Shiba
R
R
Yanagisawa
M
M
Masaki
T
T
Kimura
S
S
Yamada
K
K
Mima
T
T
Shigeno
T
T
Goto
K
K
D000818:Animals; D002118:Calcium / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; C022838:nickel chloride; D009532:Nickel; D009529:Nicardipine; D002118:Calcium