EFFECT OF SALT LOADING ON CARDIOVASCULAR HUMORAL AND ENDOTHELIAL DYSFUNCTION mRNA EXPRESSION AND REGULATION BY ANTIOXIDANTS

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ABSTRACT

This study was aimed at investigating the modulatory effects of antioxidants (Vitamin C, KV, Mg2+ and lisinopril) on the cardiovascular system and endothelial cell function in salt loaded Sprague Dawley rats. Garcinia Kola seeds was obtained commercially in Benin City, Nigeria. Extraction of KV will be achieved by the methods of Adaramoye and Medeiros (2009). Materials to be employed for this study include thirty five (35) adult male Sprague Dawley rats. The rats will be randomly selected into seven (6) experimental groups. Group 1, control rats (CR) will be fed with normal rat chow and water ad libitum. Group 2, will receive high salt diet containing 8% NaCl and water for six weeks [(salt-loaded rats (SLRs)] as described by Dennis et al., 1999. Group 3: Rats will be SLRs + kolaviron 200mg/kg bw/day concurrently for 6 weeks. Group 4: Rats will be SLRs + high (4.8mM) Magnesium (Mg2+) concurrently for a period of 6 weeks. Group 5: Rats will be SLRs + Vitamin C (100mg/kgbw/day)simultaneously for a period of 6 weeks.Group 6: Rats will be SLRs + L – Arginine (100mg/kg wt/day) nitric oxide donor.Group 7: Will be SLRs + 2.3 mg/kgbw/day Lisinopril for 6 weeks. The animals will be sacrificed and arterial blood vessels will be harvested and placed in physiological salt solution (PSS) of the following composition (mM): NaCl 119, KCl 4.7, NaHCO3 24.9, NaH2PO4 1.2, MgSO4 1.2, CaCl2 1.6, glucose 11.5. The arteries will be cleaned of adhering connective tissues and cut into 2-3mm rings for isolated tissues reactivity. Rings will be pre-contracted with EC70 M PE and /or high (80 mM K+) PSS. At stable contraction, cumulative relaxation response tests (10-9 to 10-3) to acetylcholine will be studied in normal PSS (control) (n = 6); in +E and -E rings. Protein expression will be done with standard Western blot molecular analytical method. Results will be presented as means ± SEM. Graphs and statistical analyses will be done using Graph Pad Prism version 8.4 windows statistical software. Students t-test will be carried out followed by one-way analysis of variance (ANOVA). P-values less than 0.005 (p<0.005) will be considered statistically. In conclusion, it is evident that salt loading ultimately leads to oxidative stress. Data from the present study show that salt-induced hypertension is associated with oxidative stress, involving significant changes in SOD, catalase and MDA homeostasis and endothelial dysfunction. The results shows that it is evident that salt loading ultimately leads to oxidative stress. Data from the present study show that salt-induced hypertension is associated with oxidative stress, involving significant changes in SOD, catalase and MDA homeostasis and endothelial dysfunction.

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