British journal of pharmacology
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1. Altered vasoreactivity may contribute significantly to the pathogenesis of diabetic vascular complications. This study investigated the effect of (a) insulin-related diabetes, and (b) chronic in vivo administration of N(omega)-nitro-L-arginine ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on mean arterial pressure and in vitro vascular reactivity to noradrenaline in mesenteric arterial bed preparations from spontaneously diabetic, insulin-dependent and treated BB rats, the best animal model of insulin-dependent mellitus (IDDM) currently available. ⋯ However, following chronic L-NAME treatment, diabetic BB/E rats exhibit attenuated hypertension and an absence of enhanced vascular responsiveness to noradrenaline in vitro compared to similarly treated non-diabetic rats. These results, together with the significantly impaired endothelium-dependent vasodilatation and unchanged endothelium-independent vasodilatation in vitro of preparations from diabetic BB/E rats, are consistent with the hypothesis that functional changes in the synthesis and metabolism of NO (rather than altered vascular responsiveness to NO) occur in diabetes. Our results indicate that good glycaemic control alone is insufficient to prevent these abnormalities in NO availability and further studies to characterize the origin of these changes are necessary.
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Comparative Study
Comparative effects of L-NOARG and L-NAME on basal blood flow and ACh-induced vasodilatation in rat diaphragmatic microcirculation.
1. The effects of N omega-nitro-L-arginine (L-NOARG) and N omega-nitro-L-arginine methyl ester (L-NAME) on diaphragmatic microcirculation in male Sprague-Dawley rats were assessed under basal conditions and after acetylcholine (ACh) stimulation. In addition, L-arginine (L-arg) was used with the aim of preventing L-NOARG and L-NAME from inhibiting ACh-induced vasodilatation, in order to explore the possibility that L-NOARG is not only a nitric oxide (NO) synthase inhibitor but also a muscarinic receptor antagonist. 2. ⋯ In conclusion, an increase in endothelium-dependent blood flow stimulated by ACh may occur in diaphragmatic microcirculation of anaesthetized rats independently of low baseline NO activity. The results also suggest that L-NAME has muscarinic receptor antagonist action in addition to its ability to inhibit NO synthase. Thus, we suggest that L-NAME should not be used as a specific NO synthase inhibitor in the rat diaphragm in situations in which there is potential for muscarinic receptors to be stimulated.