A possible indirect sympathomimetic action of metformin in the arterial vessel wall of spontanously hypertensive rats

Lee, JiHun M.; Peuler, Jacob D.

doi:10.1016/s0024-3205(01)01202-4

Cited by 16 publications

(13 citation statements)

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“…Several studies have demonstrated that patients with type 2 DM not only have increased levels of circulating markers of free radicalinduced damage, but also reduced antioxidant defenses (Lee and Peuler, 2001;Long et al, 2000;Lapidot et al, 2002). For instance, one study demonstrated the exposure of mesangial and other cell types to high glucose levels leading to an increase in ROS such as hydrogen peroxide, superoxide anion, and hydroxyl radicals (Martin-Gallan et al, 2003;Brownlee, 2001Brownlee, , 2005.…”

Section: Discussionmentioning

confidence: 99%

Baicalin upregulates the genetic expression of antioxidant enzymes in Type-2 diabetic Goto-Kakizaki rats

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Baicalin upregulates the genetic expression of antioxidant enzymes in Type-2 diabetic Goto-Kakizaki rats

et al. 2011

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“…Metformin reduced arterial pressure in spontaneously hypertensive rats (Bhalla et al. , 1996), and rapidly relaxed contractions to adrenoceptor agonists in aortic rings from spontaneously hypertensive rats (Lee and Peuler, 2001). Metformin corrected the altered endothelium‐dependent response of resistance arteries to vasodilator agents in diabetic rats (Sartoretto et al.…”

Section: Discussionmentioning

confidence: 99%

Protective role of the antidiabetic drug metformin against chronic experimental pulmonary hypertension

Agard

Rolli–Derkinderen

Roque

et al. 2009

British J Pharmacology

117

100

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Background and purpose: Pulmonary arterial hypertension (PAH) is associated with increased contraction and proliferation of pulmonary vascular smooth muscle cells. The anti‐diabetic drug metformin has been shown to have relaxant and anti‐proliferation properties. We thus examined the effect of metformin in PAH. Experimental approach: Metformin effects were analysed in hypoxia‐ and monocrotaline‐induced PAH in rats. Ex vivo and in vitro analyses were performed in lungs, pulmonary artery rings and cells. Key results: In hypoxia‐ and monocrotaline‐induced PAH, the changes in mean pulmonary arterial pressure and right heart hypertrophy were nearly normalized by metformin treatment (100 mg·kg−1·day−1). Pulmonary arterial remodelling occurring in both experimental models of PAH was also inhibited by metformin treatment. In rats with monocrotaline‐induced PAH, treatment with metformin significantly increased survival. Metformin increased endothelial nitric oxide synthase phosphorylation and decreased Rho kinase activity in pulmonary artery from rats with PAH. These effects are associated with an improvement of carbachol‐induced relaxation and reduction of phenylephrine‐induced contraction of pulmonary artery. In addition, metformin inhibited mitogen‐activated protein kinase activation and strongly reduced pulmonary arterial cell proliferation during PAH. In vitro, metformin directly inhibited pulmonary artery smooth muscle cell growth. Conclusions and implications: Metformin protected against PAH, regardless of the initiating stimulus. This protective effect may be related to its anti‐remodelling property involving improvement of endothelial function, vasodilatory and anti‐proliferative actions. As metformin is currently prescribed to treat diabetic patients, assessment of its use as a therapy against PAH in humans should be easier.

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“…Activation of ␣ 1 -adrenoceptors on adrenal medulla in the regulation of ␤-endorphin secretion has also been mentioned (19). In fact, it has been proposed that metformin releases norepinephrine by an indirect sympathomimetic-like action (39). Also, metformin inducing the release of norepinephrine from postganglionic sympathetic nerve endings (40) has been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Novel Mechanism for Plasma Glucose–Lowering Action of Metformin in Streptozotocin-Induced Diabetic Rats

et al. 2006

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To better understand the insulin-independent plasma glucose-lowering action of metformin, we used streptozotocin (STZ)-induced diabetic rats to investigate the possible mechanisms. Oral intake of metformin decreased the plasma glucose of STZ-induced diabetic rats with a parallel increase of plasma ␤-endorphin-like immunoreactivity (BER). Mediation of opioid -receptors in the action of metformin was identified by the blockade of receptors with antagonist in STZ-induced diabetic rats and the failure of action in opioid -receptor knockout diabetic mice. Release of BER from adrenal glands by metformin was characterized, using bilateral adrenalectomy and the release of BER from isolated adrenal medulla of STZ-induced diabetic rats. Repeated treatment with metformin in STZ-induced diabetic rats increased the mRNA and protein levels of GLUT-4 in soleus muscle that was blocked by naloxonazine. Reduction of the mRNA or protein levels of hepatic PEPCK was also impeded in the same group of STZ-induced diabetic rats. In conclusion, our results provide novel mechanisms for the plasma glucose-lowering action of metformin, via an increase of ␤-endorphin secretion from adrenal glands to stimulate opioid -receptor linkage, leading to an increase of GLUT-4 gene expression and an attenuation of hepatic PEPCK gene expression in STZinduced diabetic rats. Diabetes 55:819 -825, 2006

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A possible indirect sympathomimetic action of metformin in the arterial vessel wall of spontanously hypertensive rats

Cited by 16 publications

References 0 publications

Baicalin upregulates the genetic expression of antioxidant enzymes in Type-2 diabetic Goto-Kakizaki rats

Baicalin upregulates the genetic expression of antioxidant enzymes in Type-2 diabetic Goto-Kakizaki rats

Protective role of the antidiabetic drug metformin against chronic experimental pulmonary hypertension

Novel Mechanism for Plasma Glucose–Lowering Action of Metformin in Streptozotocin-Induced Diabetic Rats

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