Regional differentiation in the rat aorta: effects of cyclooxygenase inhibitors

1997 ◽  
Vol 273 (3) ◽  
pp. H1478-H1483 ◽  
Author(s):  
D. Schachter ◽  
J. C. Sang
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Cyclic Nucleotide ◽  
Rat Aorta ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Cyclooxygenase Inhibitors ◽  
Regional Differentiation ◽  
Phosphodiesterase Activity ◽  
Dynamic Regulation

Rat aortic endothelium is differentiated regionally for signaling the underlying smooth muscle via nitric oxide to increase the level of guanosine 3',5'-cyclic monophosphate (cGMP) [R.E. Abbott and D. Schachter. Am. J. Physiol. 266 (Heart Circ. Physiol. 35): H2287-H2295, 1994]. Maximal activity is just distal to the aortic arch, i.e., in the "windkessel" region, and diminishes peripherally. This report describes the same pattern of endothelial differentiation for a second signal arising from the cyclooxygenase arm of the eicosanoid pathway. Treatment of sequential segments of rat aorta in vitro with indomethacin (50 microM) or acetylsalicylate (100 microM) increased the cGMP content selectively in aortic segments prepared from the windkessel region. The indomethacin effect was eliminated by denuding the endothelium or by inhibiting cyclic nucleotide phosphodiesterase activity. Prostaglandin H2 was identified as a cyclooxygenase product involved in this signal pathway because treatment with the compound decreased cGMP levels, and this effect was eliminated by inhibiting cyclic nucleotide phosphodiesterase activity. Endothelial regulation of smooth muscle cGMP via nitric oxide and cyclooxygenase pathways supports the concept of dynamic regulation of aortic wall properties in the windkessel region.

Regional differentiation in rat aorta: L-arginine metabolism and cGMP content in vitro

1994 ◽  
Vol 266 (6) ◽  
pp. H2287-H2295 ◽  
Author(s):  
R. E. Abbott ◽  
D. Schachter
Keyword(s):  
Nitric Oxide ◽  
Ambient Medium ◽  
Rat Aorta ◽  
Regional Differentiation ◽  
Arginine Metabolism ◽  
Regional Pattern ◽  
Aortic Endothelial Cells ◽  
Arginine Uptake ◽  
Oxide Synthase

Sequential segments of rat aorta incubated in vitro exhibit a characteristic activity pattern for the metabolism of L-arginine, the substrate for nitric oxide synthase, and for the content of guanosine 3',5'-cyclic monophosphate (cGMP), the mediator of nitric oxide relaxation of vascular smooth muscle. Highest values were observed just distal to the arch and diminish peripherally. Prior removal of the endothelium, treatment with ouabain, or replacement of ambient medium Na+ decreased L-arginine uptake and metabolism and eliminated the pattern of regional differentiation. Removal of endothelium reduced the cGMP content with loss of the regional pattern. A favorable extracellular/intracellular Na+ gradient is required for the moiety of L-arginine uptake destined for metabolism in the endothelial cell. Replacement of ambient Na+ or treatment with ouabain also decreases markedly the L-arginine metabolism and uptake in cultured rat aortic endothelial cells. When aortic segments were tested with five additional substances, L-leucine uptake alone followed a regional pattern similar to that for L-arginine, and no such pattern was observed for the uptake of L-alanine, alpha-aminoisobutyrate, 3-methylglucose, or Ca2+.

Regional differentiation in the rat aorta for a novel signaling pathway: leucine to glutamate

1997 ◽  
Vol 273 (3) ◽  
pp. H1484-H1492 ◽  
Author(s):  
D. Schachter ◽  
J. C. Sang
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Human Peripheral Blood ◽  
Umbilical Vein ◽  
Rat Aorta ◽  
Signal Pathway ◽  
Regional Differentiation ◽  
Differentiation Pattern ◽  
Cells Cultured

Rat aortic endothelium is differentiated regionally for regulating guanosine 3',5'-cyclic monophosphate (cGMP) levels in underlying smooth muscle by signaling via nitric oxide and prostaglandin H2. Highest activity is just distal to the aortic arch and diminishes peripherally. The same differentiation pattern is reported here for a third and novel signal pathway: endothelial conversion of L-leucine to L-glutamate. Sequential segments of rat aorta incubated in vitro convert L-[U-14C]leucine to a major 14C metabolite identified as L-glutamate. Net synthesis of glutamate is greatest in aortic segments of the "windkessel" region; significant quantities are also observed in the pancreas, testis, and lung but very little in 10 additional tissues. Endothelial cells cultured from mouse brain, human umbilical vein, or bovine aorta and human peripheral blood macrophages also form [14C]glutamate. When aortic segments are denuded of endothelium, treatment with L-glutamate in the presence of 3-isobutyl-1-methylxanthine significantly increases the cGMP content. A number of leucine derivatives inhibit the leucine-to-glutamate conversion and decrease the cGMP content in aortic segments in vitro.

The basal endothelial inhibitory influence on vascular tone is not affected in nitroglycerin-tolerant rat aorta

1994 ◽  
Vol 72 (9) ◽  
pp. 1094-1097 ◽  
Author(s):  
J. Van de Voorde ◽  
S. Vyt ◽  
B. Vanheel
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Vascular Tone ◽  
Prolonged Exposure ◽  
Rat Aorta ◽  
Nitrate Tolerance ◽  
Inhibitory Influence ◽  
And Control

Prolonged exposure to nitrovasodilators produces tolerance and dependence. Nitrovasodilators exert their action on vascular smooth muscle cells by activation of guanylyl cyclase. Nitrates share this mechanism with endothelial NO, which exerts a continuous inhibitory influence on vascular tone. Whether the basal inhibitory endothelial influence might be affected in rat aorta exposed in vitro to a tolerance-inducing concentration of nitroglycerin was investigated in this study. It was found that the basal inhibitory influence, assessed as its inhibitory influence on norepinephrine-induced contraction, and as the contractile effect of N-nitro-L-arginine methyl ester or methylene blue, was the same in nitroglycerin-tolerant and control aortic rings. Our results give an indication that changes in basal inhibitory endothelial influence are not involved in the phenomena of nitrate tolerance and nitrate dependence.Key words: nitroglycerin, nitrates, tolerance, endothelium, nitric oxide.

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