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355
IJC 0543D
Diuretic effect of metoprolol
S.R. Mittal, A.K. Mathur, S. Vanjani
J. L.N. Medical College and Hospital, Ajmer (Rajasthan), India
(Received 12 November 1986; accepted 8 December 1986)
Metoprolol caused a significant (P < 0.001) increase in urine output in rabbits. There was no change in serum sodium concentration but serum potassium levels increased significantly. The most probable mechanism of action was increase in renal blood flow and glomerular filtration rate.
Key words: Metoprolol: Diuretic: Serum potassium; Renal blood flow
Introduction
Two of our patients with mild hypertension complained of marked polyuria when started on metoprolol monotherapy (50 mg twice a day). Repeated stopping and restarting the drug and a change in the proprietary preparation confirmed the symptoms to be related to
metoprolol ingestion. Therefore we decided to evaluate the diuretic potentiality of metopro- 101. As it was not possible to maintain fixed fluid intake and environmental temperature in
patients over several days and as concurrent disease, drug therapy and renal function could affect the results, we decided to perform an animal study.
Material and Method
Five rabbits were put in metabolic cages and were kept in a room with nearly constant temperature. They were given the same diet throughout the study and water intake was also kept constant. Urine output was measured daily for eight days to find the mean 24-hour
urinary output for each rabbit. From the ninth day each rabbit was given 3 mg/kg of metoprolol in two equally divided doses orally for eight days and daily urine output measurement was continued. Serum sodium and potassium concentrations were measured in
each rabbit before starting metoprolol and on last day of therapy.
Results
The results are shown in Table 1. There was a statistically significant increase in urine output during metoprolol therapy. Mean serum sodium and potassium concentrations before therapy were 141 f 3 mEq/l and 4.05 f 0.25 mEq/l, respectively. On the last day of therapy respective values were 145 + 3.5 mEq/l and 6.15 f 0.15 mEq/l.
Correspondence to: Dr. S.R. Mittal, X1/101. Brahampuri. Ajmer (Rajasthan), India-Pin-305 001.
International Journal of Cardiology, 15 (1987) 355-356 ‘a Elsevier Science Publishers B.V. (Biomedical Division)
356
TABLE 1
Rabbit Mean of 8 days urine
output (ml) before
metoprolol
Mean of 8 days urine
output (ml) during
metoprolol therapy
(3 m8/k8)
Mean increase in
urine output (ml)
1 59.50 92.00 32.50 2 62.25 113.5 51.25 3 86.37 133.8 47.43 4 67.12 99.0 31.88 5 93.00 118.4 25.40
Combined 73.64 ml 113.34 ml 37.69 ml f 4.96 (SE) mean P i 0.001
Discussion
Metoprolol being beta, selective does not block beta, receptor dependent vasodilatation of renal vessels. It also has maximum anti-renin activity as compared to atenolol and
propranolol [l]. Being lipophilic it also acts through central nervous system beta receptors. These various factors could cause a relative improvement in renal blood flow and glomerular filtration. The effect is likely to be variable because of marked interpatient variability in
bioavailability of metoprolol [2] and serum renin levels. Although a marked diuretic effect as observed in two of our cases is likely to be
uncommon, our experimental observations suggest that the drug is likely to have some degree
of diuretic effect in all cases. Raised serum potassium during metoprolol therapy is a combined effect of aldosterone suppression and blockade of beta receptor mediated uptake of
potassium in the muscles [3].
Acknowledgements
We are grateful to Dr. S.K. Sharma, Professor and Head of the Department of Pharmacol- ogy and Dr. G. Agarwal for their suggestions, guidance and assistance.
References
1 Keeton TK, Campbell WB. The pharmacologic alteration of renin release. Pharmacol Rev
1981;31:81-227.
2 Wood AJJ. Pharmacologic differences between beta blockers. Am Heart J 1984;108:1070-1077.
3 Traub YM, Rabinov M, Rosenfeld JB, Treuherz S. Elevation of serum potassium during beta
blockade. Clin Pharmacol Ther 1980;28:765-768.
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