Effects of the chronic in vivo administration of L-NAME on the contractile responses of the rat perfused mesenteric bed.
The effects of the chronic in vivo inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine methyl ester (L-NAME) on vascular contractility were studied in the rat perfused mesenteric bed. The chronic treatment with L-NAME during 4 weeks induced a rise in systolic blood pressure (basal: 115.1 +/- 6.5 mmHg; chronic L-NAME treatment: 171.7 +/- 7.7 mmHg, n = 16, P < 0.05). After the chronic NOS inhibition, the potentiation of the maximal vasoconstrictor responses to noradrenaline, phenylephrine and KCl was to the same extent as that observed after the in vitro exposure to 100 microM L-NAME. No further potentiation of the contractile responses was achieved when the mesenteric beds isolated from L-NAME treated rats were incubated in vitro with 100 microM L-NAME. The endothelium removal but not the inhibition of prostanoid synthesis with either 10 microM indomethacin or 10 microM 17-octadecynoic acid potentiated the contractions to noradrenaline and to KCl both under control conditions as well as after the chronic in vivo administration of L-NAME. These observations taken together suggest that after chronic L-NAME maximum inhibition of nitric oxide synthase was achieved and no compensatory mechanisms able to counterbalance the increase in contractile responses were developed. Further studies are necessary to elucidate the nature of the factors, other than nitric oxide, that contribute to the potentiation of contractile responses observed when the endothelium is removed after L-NAME treatment.
Mendizabal
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VE
Instituto de Investigaciones Farmacológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Feleder
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EC
Adler-Graschinsky
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E
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011189:Potassium Chloride; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin