Age-related disappearance of the inhibitory effect of vascular endothelium on agonist-induced vasoconstriction in rat mesenteric vascular beds.
We previously reported that endothelium-derived hyperpolarizing factor (EDHF)-mediated response time-dependently suppressed methoxamine-induced vasoconstriction in mesenteric vascular beds isolated from 8-week-old rats. We investigated age-related changes in endothelial regulation of methoxamine-induced vasoconstriction. Mesenteric vascular beds isolated from young (8-week-old) to adult (16-week-old) rats were perfused, and changes in perfusion pressure induced by continuous perfusion of methoxamine or high KCl (60 mM) were measured over 180 min. In young preparations with intact endothelium, methoxamine-induced vasoconstriction time-dependently decreased to 20% of the initial levels, while time-dependent reduction was not observed in adult preparations. High KCl-induced vasoconstriction in young and adult preparations did not show time-dependent reduction. Endothelium removal abolished time-dependent reduction of methoxamine-induced vasoconstriction in young preparations and significantly attenuated vasoconstriction in adult preparations. Indomethacin, seratrodast, or tempol but not catalase significantly reduced methoxamine-induced vasoconstriction in adult preparations with endothelium. A23187 (Ca(2+)-ionophore)-, but not acetylcholine-, induced endothelium-dependent vasodilation in the presence of N(G)-L-nitro arginine methyl ether in adult preparations was significantly smaller than that in young preparations. These findings suggest that the inhibitory effect of mesenteric vascular endothelium on methoxamine-induced vasoconstriction disappears with aging by reducing EDHF and increasing endothelium-derived contracting factors and reactive oxygen species.
Jin
Xin
X
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
Satoh-Otonashi
Yukiko
Y
Zamami
Yoshito
Y
Hobara
Narumi
N
Koyama
Toshihiro
T
Sun
Pengyuan
P
Li
Simin
S
Kitamura
Yoshihisa
Y
Kawasaki
Hiromu
H
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D001685:Biological Factors / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006538:Heptanoic Acids / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000528:radiation effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D016227:Benzoquinones; D001685:Biological Factors; D003497:Cyclic N-Oxides; D006538:Heptanoic Acids; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D003840:Deoxycholic Acid; D000001:Calcimycin; C060230:seratrodast; D011189:Potassium Chloride; D002374:Catalase; D008729:Methoxamine; D000109:Acetylcholine; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin