EFFECT OF TIENOXOLOL, A NEW DIURETIC BETA-BLOCKING AGENT, ON URINARY PROSTAGLANDIN EXCRETION IN THE RAT

1 The effects of tienoxolol, (ethyl 2-[3-[(1, 1 yl)amino]-2-hydroxypro poxyl-5-[(2-thienylcarbonyl) amino] benzoate, hydrochloride), a novel drug exhibiting both diuretic and beta-adrenoceptor blocking propertie s, were investigated on urinary 6-keto-prostaglandin F1alpha (6-keto-P GF1alpha) and PGE2 excretion in the rat and compared to those of refer ence diuretic (furosemide) and beta-adrenoceptor antagonists (acebutol ol, propranolol). Since tienoxolol was shown to bind to A1 and A2 aden osine receptors, the action of theophylline was also evaluated. 2 Tien oxolol (8-128 mg kg-1, p.o.) induced a dose-related increase of 6-keto -PGF1alpha excretion from 32 mg kg-1 but a significant elevation of ur inary PGE2 levels was only reached after administration of 128 mg kg-1 . However, renal prostaglandin concentrations were not modified by tie noxolol. 3 Furosemide (32 mg kg-1) displayed a strong diuretic activit y but did not enhance 6-keto-PGF1alpha excretion. Likewise, the latter was unaffected by acebutolol and propranolol (I 28 mg kg-1) and no si gnificant diuresis was observed following administration of these two beta-blocking agents. Theophylline (64 mg kg-1), like tienoxolol, was able to induce both diuresis and urinary prostaglandin excretion. Furt hermore, they bound with similar affinities to A1 and A2 adenosine rec eptors. This led to the suggestion that a relationship between P1-puri noceptors, prostaglandin release, diuresis and natriuresis could exist . 4 Oral co-administration of NECA (0.2 mg kg-1 with tienoxolol marked ly reduced the urinary 6-keto-PGF1alpha excretion observed when tienox olol was administered alone. However, neither diuresis nor natriuresis were modified, demonstrating that the proposed relationship was unten able. 5 In conclusion, PGI2 Probably does not participate in the diure tic and natriuretic activity of tienoxolol. The increase of urinary 6- keto-PGF1alpha excretion may result not only from the haemodynamic pro perties of the drug but also from the rise of the urinary flow induced by tienoxolol.