Effect of chronic lithium administration on endothelium-dependent relaxation of rat mesenteric bed: role of nitric oxide

Abstract

The mechanism of action of lithium, an effective treatment for bipolar disease, is still unknown. In this study, the mesenteric vascular beds of control rats and rats that were chronically treated with lithium were prepared by the McGregor method, and the mesenteric vascular bed vasorelaxation responses were examined. NADPH-diaphorase histochemistry was used to determine the activity of NOS (nitric oxide synthase) in mesenteric vascular beds. We demonstrated that ACh-induced vasorelaxation increased in the mesenteric vascular bed of rats treated with lithium. Acute No-nitro-L-arginine methyl ester (L-NAME) administration in the medium blocked ACh-induced vasorelaxation in the control group more effectively than in lithium-treated rats, while the vasorelaxant response to sodium nitroprusside, a NO donor, was not different between lithium-treated and control groups. Acute aminoguanidine administration blocked ACh-induced vasorelaxation of lithium-treated rats, but had no effect in the control rats. Furthermore, NOS activity, determined by NADPH-diaphorase staining, was significantly greater in the mesenteric vascular beds from chronic lithium-treated rats than in those from control rats. These data suggest that the enhanced ACh-induced endothelium-derived vasorelaxation in rat mesenteric bed from chronic lithium-treated rats might be associated with increased NOS activity, likely via iNOS. Simultaneous acute L-NAME and indomethacin administration suggests the possible upregulation of EDHF (endothelium-derived hyperpolarizing factor) in lithium-treated rats.

Low-Dose Lithium Stabilizes Human Endothelial Barrier by Decreasing MLC Phosphorylation and Universally Augments Cholinergic Vasorelaxation Capacity in a Direct Manner

“…In light of our current findings, lithium at low therapeutic concentrations functionally represented a universal endothelium protective agent, as reported by others in single species and only one vascular province (Bakken et al, 1992; Afsharimani et al, 2007; Rahimzadeh-Rofouyi et al, 2007). The last of these studies, e.g., found that low lithium concentrations (0.5 mmol/L) reduced and higher ones (2 mmol/L) improved ACH-induced mesenteric vascular bed relaxation, which is partly at odds with our results, perhaps because of the mesenteric vessel type used (Rahimzadeh-Rofouyi et al, 2007).…”

“…First, we wanted to clarify whether low concentrations of lithium help support endothelium-dependent vessel relaxation, since conflicting results had previously been published (Bakken et al, 1992; Afsharimani et al, 2007; Rahimzadeh-Rofouyi et al, 2007; Bosche et al, 2016). Second, we wanted to assess whether low concentrations of lithium carbonate, as a commonly used drug in bipolar disorder and other psychiatric/neurological conditions (Geddes and Miklowitz, 2013; Yatham et al, 2013), correspondingly augment endothelium-dependent thoracic and cerebral vessel relaxation capacity.…”

“…Taken together, there is accumulating evidence indicating that lithium may have protective effects also on vessel function. On the other hand, conflicting results have been published for the impact of low lithium concentrations on vascular and endothelial functions; then human data are lacking almost completely (Bakken et al, 1992; Afsharimani et al, 2007; Rahimzadeh-Rofouyi et al, 2007; Yoo and Kim, 2009; Bosche et al, 2016). Furthermore, there is surprisingly no human data investigating whether low-dose lithium can actually improve endothelial dynamic barrier functioning.…”

Mechanisms of nitric oxide-mediated, neurogenic vasodilation in mesenteric resistance arteries of toad Bufo marinus

“…In contrast, positive NADPH-diaphorase staining, typical of eNOS, was observed in the endothelium of rat mesenteric arteries, as has been previously reported ( Fig. 1B) (1,4). In contrast to the endothelium of toad, positive NADPH-diaphorase histochemical staining was observed in nerve fibers located throughout the mesentery ( Fig.…”

“…Tissues were evaluated for NADPH-diaphorase staining (formazan precipitates) using a light microscope (Zeiss) and photographed with a digital imaging system (Spot 35 camera system) (6). Mesenteric arteries from rats were used as a control to demonstrate the presence of NOS in the vascular endothelium, as has been previously demonstrated (1,4). nNOS immunohistochemistry.…”