The effect of cold immobilisation stress on brain MAO-A inhibitory activity and pinealN-acetylserotonin and melatonin in spontaneously hypertensive and normotensive rats

This paper will review our recent data relevant to the antioxidant effects of N-acetylserotonin (NAS), the immediate precursor of melatonin, the pineal gland indole. Mechanisms of the antioxidant effects of NAS might involve interaction with melatonin type 3 receptors and nonreceptor mechanisms such as stimulation of glutathione peroxidase, an antioxidant enzyme; inhibition of lipid peroxidation; suppression of phospholipase A2 activation; attenuation of tumor necrosis factor-alpha production; prevention of pathological opening of the mitochondrial permeability transition pores; and inhibition of sepiapterin reductase, the key enzyme of biosynthesis of tetrahydrobiopterin, the essential cofactor of nitric oxide synthase. NAS actions on some of these enzymes might be receptor-mediated. Protective effects of NAS against oxidative damage are independent from the effect of melatonin and, depending on the model, are 5 to 20 times stronger than that of melatonin. Antioxidant effect of NAS might underpin its cognition-enhancing, antiaging, antidepressant, antihypertensive, and antitumor effects. NAS and its derivatives might be useful in protection against oxidative stress-related disorders (cell death, mutagenesis, aging) and diseases (sepsis, cancer, postischemic trauma, Alzheimer's disease, parkinsonism).

Section: Nas In Spontaneously Hypertensive Ratsmentioning

confidence: 99%

“…Thus, the higher basal MAO-A inhibiting activity in SHR vs. WKY rats might be considered as the protective mechanism (although eventually insufficient) against the development of hypertension in SHR rats. 64…”

Section: Nas In Spontaneously Hypertensive Ratsmentioning

confidence: 99%

Antioxidant Effects of N-Acetylserotonin: Possible Mechanisms and Clinical Implications

Oxenkrug

2005

“…Melatonin attenuated pinealectomy‐induced hypertension, 25 while pinealectomy attenuated the hypotensive effect of clorgyline, a selective monoamine oxidase type A inhibitor which stimulated melatonin biosynthesis 26 . Basal activity of the endogenous monoamine oxidase‐A (MAO‐A) inhibitor was three times higher in SHR than in WKY rats 27 . Cold‐immobilization stress elevated the levels of the endogenous MAO‐A inhibitor and induced higher pineal NAS levels in SHR than in WKY rats 28 …”

Section: Introductionmentioning

confidence: 99%

Ramelteon attenuates age‐associated hypertension and weight gain in spontaneously hypertensive rats

Oxenkrug¹,

Summergrad²

2010

Self Cite

The neuroendocrine theory of aging suggests the common mechanisms of developmental (prereproductive) and aging (postreproductive) processes and identified a cluster of conditions (hypertension, obesity, dyslipidemia, type 2 diabetes, menopause, late onset depression, vascular cognitive impairment, impairment of immune defense, and some forms of cancer) as age-associated neuroendocrine disorders (AAND). Obesity, dyslipidemia, hypertension, and type 2 diabetes were later described as metabolic syndrome (MetS). Because melatonin attenuated development of MetS is age-dependent, that is, in young and old, but not in middle-aged rats, we studied the effect of the selective melatonin agonist, Ramelteon, on the two core symptoms of MetS/AAND: hypertension and body weight gain in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto male rats (WKY). SHR rats developed hypertension at the time of maximal weight gain that coincided with the onset of reproductive activity (8-10 weeks old). Chronic (but not acute) administration of Ramelteon (in drinking water, 8 mg/kg/day, from 4 to 12 weeks of age) attenuated age-associated increase of systolic blood pressure (tail-cuff method) by 45%, and age-associated body weight gain by 30%. Acute and chronic Ramelteon did not affect blood pressure and body weight in normotensive WKY rats. Ramelteon-induced attenuation of age-associated hypertension and weight gain suggests that Ramelteon might attenuate the other symptoms of MetS/AAND and might be useful in the treatment of MetS/AAND during puberty, menopause, and old age.

“…The linkage between age, hypertension, and basal, isoproterenol‐, and cold‐immobilization stress‐induced pineal NAS levels in SHR rats suggested that NAS might be the endogenous factor protecting rats from the development of hypertension 58. It is noteworthy that the basal brain MAO‐A inhibitory activity of tribulin was three times higher in SHR than in WKY rats, while no difference was found in brain MAO‐B inhibitory activity of tribulin 64. One might suggest that the development of hypertension in SHR is influenced by the MAO‐A inhibiting activity (tribulin) since the increase of this activity would facilitate formation of NAS, the alleged endogenous antihypertensive factor.…”

Section: Mechanisms Of Nas Effectsmentioning

confidence: 96%

“…One might suggest that the development of hypertension in SHR is influenced by the MAO‐A inhibiting activity (tribulin) since the increase of this activity would facilitate formation of NAS, the alleged endogenous antihypertensive factor. Thus, the higher basal MAO‐A inhibiting activity in SHR vs. WKY rats might be considered as the protective mechanism (although eventually insufficient) against the development of hypertension in SHR rats 64…”

Section: Mechanisms Of Nas Effectsmentioning

confidence: 99%

Antioxidant Effects of N‐Acetylserotonin

Oxenkrug

2005

This paper will review our recent data relevant to the antioxidant effects of N‐acetylserotonin (NAS), the immediate precursor of melatonin, the pineal gland indole. Mechanisms of the antioxidant effects of NAS might involve interaction with melatonin type 3 receptors and nonreceptor mechanisms such as stimulation of glutathione peroxidase, an antioxidant enzyme; inhibition of lipid peroxidation; suppression of phospholipase A2 activation; attenuation of tumor necrosis factor‐α production; prevention of pathological opening of the mitochondrial permeability transition pores; and inhibition of sepiapterin reductase, the key enzyme of biosynthesis of tetrahydrobiopterin, the essential cofactor of nitric oxide synthase. NAS actions on some of these enzymes might be receptor‐mediated. Protective effects of NAS against oxidative damage are independent from the effect of melatonin and, depending on the model, are 5 to 20 times stronger than that of melatonin. Antioxidant effect of NAS might underpin its cognition‐enhancing, antiaging, antidepressant, antihypertensive, and antitumor effects. NAS and its derivatives might be useful in protection against oxidative stress‐related disorders (cell death, mutagenesis, aging) and diseases (sepsis, cancer, postischemic trauma, Alzheimer's disease, parkinsonism).