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.