Effects of antenatal, postpartum and post-weaning melatonin supplementation on blood pressure and renal antioxidant enzyme activities in spontaneously hypertensive rats

Abstract

Although melatonin lowers blood pressure in spontaneously hypertensive rats (SHR), its effect following antenatal and postpartum supplementation on the subsequent development of hypertension in SHR pups remains unknown. To investigate this, SHR dams were given melatonin in drinking water (10 mg/kg body weight/day) from day 1 of pregnancy until day 21 postpartum. After weaning, a group of male pups continued to receive melatonin till the age of 16 weeks (Mel-SHR), while no further melatonin was given to another group of male pups (Maternal-Mel-SHR). Controls received plain drinking water. Systolic blood pressure (SBP) was measured at 4, 6, 8, 12 and 16 weeks of age, after which the kidneys were collected for analysis of antioxidant enzyme profiles. SBP was significantly lower till the age of 8 weeks in Maternal-Mel-SHR and Mel-SHR than that in the controls, after which no significant difference was evident in SBP between the controls and Maternal-Mel-SHR. SBP in Mel-SHR was lower than that in controls and Maternal-Mel-SHR at 12 and 16 weeks of age. Renal glutathione peroxidase (GPx) and glutathione s-transferase (GST) activities, levels of total glutathione and relative GPx-1 protein were significantly higher in Mel-SHR. GPx protein was however significantly higher in Mel-SHR. No significant differences were evident between the three groups in the activities of superoxide dismutase, catalase and glutathione reductase. In conclusion, it appears that while antenatal and postpartum melatonin supplementation decreases the rate of rise in blood pressure in SHR offspring, it however does not alter the tendency of offspring of SHR to develop hypertension.

Upregulation of catalase and downregulation of glutathione peroxidase activity in the kidney precede the development of hypertension in pre-hypertensive SHR

“…5,9,30 Our results showed no significant difference in total SOD activity (Figure 1) or in the mRNA expressions of CuZn-SOD and Mn-SOD (Table 2) between SHR and WKY rats aged between 2 and 16 weeks. This has also previously been reported by Lee et al 22 Numerous other studies too have reported similar findings of unchanged SOD activity or its protein levels in the kidneys of adult SHR. 23,30,35 Renal morphology or urine protein excretion was not examined in this study.…”

“…The main findings of this study include: (i) higher CAT activity and its relative mRNA levels in the kidneys of SHR from the age of 2 weeks (Figure 2 and Table 2), (ii) lower kidney GPx activity in SHR from the age of 3 weeks and lower relative GPx mRNA levels at 8 and 10 weeks of age ( Figure 3 and Table 2), (iii) higher renal TAS in SHR from the age of 3 weeks and onward (Table 3), (iv) higher renal MDA levels at 16 weeks (Table 3), (v) lower levels of renal H 2 O 2 in SHR from the age of 8 weeks (Table 4) and (vi) no significant difference in renal total SOD activity or the relative SOD mRNA levels of CuZn-SOD and Mn-SOD ( Figure 1 and Table 2) when compared with age-matched WKY rats. Although a significantly elevated renal CAT activity in 6-and 16-week old, 22 and older SHR 8,23 has been reported before, this is the first time that altered renal CAT expression and activity has been reported in pre-hypertensive SHR. The demonstration of higher CAT activity and its mRNA levels from as early as 2 weeks in SHR suggests that CAT expression and activity might be one of the primary abnormalities in SHR that might have a role in the pathogenesis of hypertension.…”

“…Higher TAS has been reported in 16-week-old SHR recently by us. 22 Lower renal TAS has also been previously reported in 22-week-old SHR. 32 It is possible that the higher TAS in this study might be due to the higher CAT activity as CAT has one of the highest turnover rates of all enzymes where one molecule of CAT can convert millions of molecules of H 2 O 2 to water and oxygen per second.…”

“…In addition, the use of CAT inhibitor during the pre-hypertensive stage might further elucidate the role of elevated CAT in the pathogenesis of hypertension in this species, although melatonin supplementation during the antenatal and postnatal period was found to significantly increase CAT expression and activity and delay the rise in blood pressure in hypertensive rats. 22 CAT mRNA level and its activity are usually upregulated when there is a disturbance in the oxidative status, particularly in H 2 O 2 levels. 26,27 Surprisingly, renal H 2 O 2 levels were consistently lower in SHR, particularly from 8 weeks onward (Table 4) and therefore, the raised levels of CAT may not be due to elevated H 2 O 2 .…”

Melatonin ameliorates the adverse effects of leptin on sperm

“… 43 It is also known to enhance the antioxidant activities of superoxide dismutase ( SOD ), glutathione peroxidase ( GPx ), catalase, and glutathione reductase (GR). 44 45 46 Besides this, melatonin has been shown to increase GPx protein in the kidney of spontaneously hypertensive rats (SHR), 47 and increase GPx-1 mRNA expression in human chorion, rat liver, and rat brain cortex. 48 49 50 Moreover, it also enhances the ability of cells to resist oxidative damage by inhibiting the pro-oxidant nitric oxide synthase.…”