Antihypertensive Action of Melatonin in the Spontaneously Hypertensive Rat

Kawashima, Koichiro; Miwa, Yuko; Fujimoto, Kazuko; Oohata, Hisayo; Nishino, Hiroshi; Koike, Hiroyuki

doi:10.3109/10641968709160037

Cited by 71 publications

(58 citation statements)

References 11 publications

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“…As the liver functions as the center of the intermediary metabolism it is more than possible that metabolic effects of MEL interfere with the liver metabolism. It has been proved that MEL also effects the kidney metabolism, urine production (Richardson et al 1992), and blood pressure (Kawashima et al 1987).…”

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confidence: 99%

Effect of Prolonged Melatonin Application on Metabolic Parameters and Organ Weights in Young Male and Female Sprague-Dawley rats

Marková¹,

Adámeková²,

Kubatka³

et al. 2003

Acta Vet. Brno

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Marková M., E. Adámeková, P. Kubatka, B. Bojková, E. Ahlersová, I. Ahlers: Effect of Prolonged Melatonin Administration on Metabolic Parameters and Organ Weights inYoung Male and Female Sprague-Dawley rats. Acta Vet. Brno 2003, 72: 163-173.The question of the introduction of melatonin as a drug remains still open. Especially the long term melatonin administration have to be analysed and discussed. The aim of present study was to analyze the effect of low doses of melatonin (4 µg/ml of tap water) administered for 70 days, daily from 15.00 to 08.00 h (from 08.00 to15.00 h animals were drinking tap water) on selected metabolic parameters in male and female Sprague-Dawley rats. In addition to concentration/content of triacylglycerols, phospholipids, cholesterol, malondialdehyde, glucose and glycogen in the serum and tissues, serum corticosterone and insulin, weights of selected organs, periovarial and epididymal fat and body weight were recordered. Melatonin was not administered to control groups. Oral glucose tolerance tests were carried out before melatonin administration and 9 weeks thereafter.Male and female rats aged 5 weeks were adapted to standard vivarium conditions and artificial light regimen L:D-12:12 h. The animals were fed MP diet containing 2.5 % fat at least and drank tap water or melatonin solution ad libitum. The rats were weighed twice a week and food and water intake was recorded. After 10 weeks they were sacrificed, organs and tissues were weighed and the aforementioned metabolic parameters were determined in the serum, liver, heart muscle and bone marrow (femur).Melatonin administration decreased significantly the serum triacylglycerol concentration and liver glycogen content in male rats, and it increased liver the phospholipid content in females. Melatonin did not acutely modify the values of other metabolic parameters. Prolonged melatonin administration significantly increased the weight of heart muscle and periovarial fat in females, in males significantly reduced the weight of adrenals, liver, heart muscle and epididymal fat as well as their body weight from day 19 to the end of experiment. Body weight in MEL-drinking females was similar to that in controls. Water and food intake in MEL-drinking males did not differ from controls, in females was temporarily increased in week 6.Prolonged melatonin administration did not significantly influence the glycemia level. The oral glucose tolerance test curves were normal before melatonin administration; one abnormal curve (out of 9 individuals) in the female group and 2 abnormal curves in the male group (out of 9 individuals) were recorded 9 weeks after melatonin administration. Prolonged melatonin treatment resulted in sexual differences in body weight, epididymal and periovarial fat, and heart muscle weight. Melatonin, metabolic and hormone responses, body and organ weightsAlthough pineal gland is the main site of melatonin (MEL) synthesis in mammals its synthesis has been proved in the retina, extraorbital lacrimal glands, Harder's glands...

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confidence: 99%

Effect of Prolonged Melatonin Application on Metabolic Parameters and Organ Weights in Young Male and Female Sprague-Dawley rats

Marková¹,

Adámeková²,

Kubatka³

et al. 2003

Acta Vet. Brno

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“…In hu mans, there is also evidence that melatonin may have a hypotensive effect in essential hypertensive patients [6], Pinealectomy increased blood pressure and daily urine production. Such effects were thought to involve the renin-angiotensin-aldosterone system as elevated plasma renin activity has been detected in pinealectomyinduced hypertensive rats [7], Furthermore, melatonin treatment has been shown to de crease plasma renin concentration and reduce blood pressure in spontaneously hypertensive rats [8],…”

Section: Introductionmentioning

confidence: 99%

[<sup>125</sup>l]lodomelatonin Binding Sites in Mammalian and Avian Kidneys

1993

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[^I25I]Iodomelatonin binding sites have been identified and characterized in kidneys of birds and mammals. These binding sites in the kidneys of guinea pig, duck and chicken were found to be stable, reversible, saturable, specific and of high affinity. The binding densities (B_max) of [¹²⁵I]iodomelatonin binding sites in the kidneys of guinea pig, duck and chicken ranged from 1.07 to 6.43 fmol/mg protein and the equilibrium dissociation constants (K_d) from 19.2 to 44.6 pmol/l at the middle of the light period (mid-light). It appears that [¹²⁵I]iodomelatonin binding in the kidneys of mammalian species may have lower densities compared with birds. In the mammals studied, the guinea pig kidney showed the highest [¹²⁵I]iodomelatonin binding. Pharmacological data indicated that the [¹²⁵I]iodomelatonin binding to kidneys of guinea pig, duck and chicken was highly specific to melatonin, 2-iodomelponin and 6-chloromelatonin. Diurnal variations in the B_max of [¹²⁵I]iodomelatonin binding sites were detected in the kidneys of duck and chicken with no difference in affinity. However, there was no diurnal variation in the K_d or B_max in the guinea pig kidneys. The density of [¹²⁵I]iodomelatonin binding sites in the cortex of guinea pig kidney was more than 8-fold higher than the binding in the medulla. Guanosine 5''-O-(3-thiotriphosphate) (GTPγS; 10 µmol/1) reduced the B_max and increased the K_d of [¹²⁵I]iodomelatonin binding sites in the chicken kidney. However, in the membrane preparations of the guinea pig kidney, co-incubation with GTPγS (15 µmol/l) increased the K_d with no effect on the B_max of the [¹²⁵I]iodomelatonin binding. The effects of GTPγS on the kidney [¹²⁵I]iodomelatonin binding suggest that these binding sites may couple to a G protein. The identification of [¹²⁵I]iodomelatonin binding sites in the kidneys of mammals and birds supports the possibility of melatonin acting directly on the renal system.

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“…Evidence has accumulated to indicate that melatonin, one of the pineal hormones, acts on the brain to regulate blood pressure in mammals [1][2][3][4]. For example, the hypoten sive effect of melatonin has been observed in patients with essential hypertension [2] or in vates blood pressure and reduces heart rate when injected into the cerebral ventricles [6,7], These observations suggest the possibility that the hypotensive effects of melatonin may be related to the endogenous release of brain serotonin.…”

Section: Introductionmentioning

confidence: 99%

Melatonin Decreases Brain Serotonin Release, Arterial Pressure and Heart Rate in Rats

1993

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The effects of intravenous administration of melatonin (30–60 mg/kg) or vehicle (10% alcohol) on arterial pressure, heart rate, blood gases or brain serotonin release were assessed in rats under urethane anesthesia. Administration of melatonin, but not the vehicle, produced a dose-related fall in mean arterial pressure, heart rate, or serotonin release in both the corpus striatum and the hypothalamus. Melatonin treatment had an insignificant effect on either P_aCO₂, P_aO₂ or pH. In addition, the melatonin-induced depressor responses were abolished by pretreatment with spinal transection, whereas melatonin-induced bradycardia was abolished by pretreatment with bilateral vagotomy. These results suggest that melatonin decreases brain serotonin release and results in sympathetic inhibition or parasympathetic stimulation which leads to hypotension and bradycardia in rats.

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Antihypertensive Action of Melatonin in the Spontaneously Hypertensive Rat

Cited by 71 publications

References 11 publications

Effect of Prolonged Melatonin Application on Metabolic Parameters and Organ Weights in Young Male and Female Sprague-Dawley rats

Effect of Prolonged Melatonin Application on Metabolic Parameters and Organ Weights in Young Male and Female Sprague-Dawley rats

[<sup>125</sup>l]lodomelatonin Binding Sites in Mammalian and Avian Kidneys

Melatonin Decreases Brain Serotonin Release, Arterial Pressure and Heart Rate in Rats

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