Changes in the regulation by endothelium of norepinephrine response in isolated, perfused mesenteric vascular bed of rats at different ages.
Age-related changes of norepinephrine response were studied in isolated perfused mesenteric arteries and veins of rats at 4, 32 and 75 weeks of age. Norepinephrine (0.1-100 nmole) significantly and dose-dependently increased perfusion pressure of the arteries, whereas it only slightly changed that of the veins. The arterial response increased, but the venous response decreased with age. Indomethacin at 5 x 10(-6) M did not change the arterial response at any of the ages. The combination of indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) at 5 x 10(-6) M, and endothelium denudation similarly augmented the response in 4-week-old rats, but neither of these affected the responses in 32- and 75-week-old rats. At raised tone by 100 mM potassium chloride, acetylcholine-induced decrease in perfusion pressure and inhibition of the response by L-NAME were attenuated gradually with age. The raised tone in 75-week-old rats was higher than that in either 4- or 32-week-old rats, but the difference disappeared in the presence of L-NAME. These results demonstrate that the arterial portion is predominant in norepinephrine response and the arterial and venous responses change oppositely with age. It is also suggested that neither prostanoids nor endothelial nitric oxide regulate the arterial response in mature animals, while only in 4-week-old rats, nitric oxide may counteractively regulate the response. Additionally, the roles of nitric oxide in the regulation of transient norepinephrine response, in the regulation of the potassium-induced tonic contracture, and in the vasodilation through muscarinic receptor stimulation seem to change somewhat differently with age.
Konishi
C
C
Laboratory of Pharmacology, Hatano Research Institute, Food and Drug Safety Center, Hadano, Kanagawa, Japan.
Naito
Y
Y
Ohara
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008642:Mesenteric Veins / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D000109:Acetylcholine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin