Effect of tienoxolol, a new diuretic beta-blocking agent, on urinary prostaglandin excretion in the rat. British journal of pharmacology. [Br J Pharmacol] Journal article | | Title | Effect of tienoxolol, a new diuretic beta-blocking agent, on urinary prostaglandin excretion in the rat. | | Author(s) | Caussade F, Cloarec A | | Institution | Laboratoires UPSA, Rueil-Malmaison, France. | | Source | Br J Pharmacol 1993 May; 109(1):278-84. | | MeSH | 6-Ketoprostaglandin F1 alpha
Adenosine
Adenosine-5'-(N-ethylcarboxamide)
Adrenergic beta-Antagonists
Animals
Brain Chemistry
Dinoprostone
Diuresis
Epoprostenol
Furosemide
Male
Natriuresis
Propanolamines
Prostaglandins
Radioimmunoassay
Radioligand Assay
Rats
Rats, Inbred Strains
Receptors, Purinergic
Theophylline
Vasodilator Agents
| | Abstract | 1. The effects of tienoxolol, (ethyl 2-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-5- [(2-thienylcarbonyl) amino] benzoate, hydrochloride), a novel drug exhibiting both diuretic and beta-adrenoceptor blocking properties, were investigated on urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and PGE2 excretion in the rat and compared to those of reference diuretic (furosemide) and beta-adrenoceptor antagonists (acebutolol, propranolol). Since tienoxolol was shown to bind to A1 and A2 adenosine receptors, the action of theophylline was also evaluated. 2. Tienoxolol (8-128 mg kg-1, p.o.) induced a dose-related increase of 6-keto-PGF1 alpha excretion from 32 mg kg-1 but a significant elevation of urinary PGE2 levels was only reached after administration of 128 mg kg-1. However, renal prostaglandin concentrations were not modified by tienoxolol. 3. Furosemide (32 mg kg-1) displayed a strong diuretic activity but did not enhance 6-keto-PGF1 alpha excretion. Likewise, the latter was unaffected by acebutolol and propranolol (128 mg kg-1) and no significant 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. Furthermore, they bound with similar affinities to A1 and A2 adenosine receptors. This led to the suggestion that a relationship between P1-purinoceptors, prostaglandin release, diuresis and natriuresis could exist. 4. Oral co-administration of NECA (0.2 mg kg-1) with tienoxolol markedly reduced the urinary 6-keto-PGF1 alpha excretion observed when tienoxolol was administered alone. However, neither diuresis nor natriuresis were modified, demonstrating that the proposed relationship was untenable.(ABSTRACT TRUNCATED AT 250 WORDS) | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 8098641 |
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