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Evaluation of diuretic, saluretic and natriuretic activity of hydrochlorothiazide in combination with misoprostol in Wistar rats

Padmavathi Shanmuganathan, Manimekalai Kumarappan.




Abstract

Background: Renal vasodilatation by prostaglandins is well proven facts. Furosemide is better diuretics due to their additional effect on intrarenal hemodynamic changes brought about by increase in local prostaglandin synthesis. No such changes occur with thiazide group of diuretics. Hence, we want to analyze the diuretic effect of hydrochlorothiazide in combination with prostaglandin analog misoprostol.

Aims and Objectives: This study aims to evaluate the diuretic, saluretic, and natriuretic activity of hydrochlorothiazide in combination with misoprostol.

Materials and Methods: Four groups of Wistar rats with six animals in each group were grouped. One group served as the control and the other three groups received furosemide, hydrochlorothiazide, and hydrochlorothiazide with misoprostol, respectively. Urine output, urinary electrolytes, saluretic activity, and natriuretic of all groups were estimated and then compared with the standard and control groups.

Results: There was a statistically difference in the urinary output between groups as determined by oneway ANOVA (F = 33.413, P ≤ 0.001 and F =260.267, P = 0.001) at 5 and 24 h, respectively. The Lipschitz value showed that standard group and test Group 4 indices were >2.0 showing potent diuretic action. There was a statistically significant difference in the urinary excretion of all the electrolytes between groups as determined by one-way ANOVA (F = 645.087, P ≤ 0.001; F = 360.49, P ≤ 0.001; and F = 366.974, P ≤ 0.001) for the levels of Na+, K+, and Cl−, respectively. It has been found that the saluretic activity was significant in all three groups when compared with control group. However, they do not show significant changes in natriuretic activity.

Conclusion: This study has shown that the diuretic activity and diuretic index of hydrochlorothiazide can be increased when it is given in combination with prostaglandin analog misoprostol and also found to be almost equivalent to standard drug furosemide effect. There was also a significant effect in the excretion of electrolytes in urine and significant saluretic activity that favors their use in edematous conditions. Saluretic activity of hydrochlorothiazide with misoprostol was also similar to furosemide. Since both the drugs are already approved and safely used for many decades, we can further do a clinical trial to confirm these findings and can be used as a combination of old drugs for a new indication.

Key words: Diuretic Index; Misoprostol; Hydrochlorothiazide; Furosemide






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