Effects of tertatolol on renal function in the isolated perfused rat kidney.
Tertatolol, a new beta-adrenergic blocker, increases glomerular filtration rate (GFR) and renal plasma flow (RPF), and enhances diuresis and natriuresis in experimental animals and humans. The mechanism underlying the renal effects of tertatolol has not been established. In the present study we addressed the possibility that tertatolol influences renal function by a direct intrarenal mechanism. For this purpose we used a preparation of isolated rat kidney perfused with an artificial cell-free medium. Tertatolol when given as a bolus injection into the renal artery at the dose of 25 and 50 micrograms/kg, but not of 12.5 micrograms/kg, significantly enhanced the glomerular filtration rate (GFR) and perfusate flow rate (PFR). In contrast, the intrarenal bolus injection of different doses of propranolol (100, 250, or 500 micrograms/kg) was unable to change GFR and PFR to a significant extent. While no change in urine flow rate was found when the lowest dose of tertatolol was used, the compound at the dose of 25 and 50 micrograms/kg progressively increased urine flow during the time of perfusion. A similar effect of tertatolol was observed for urinary sodium and potassium excretion. In contrast, different doses of propranolol did not significantly change the urine flow rate or sodium and potassium excretion rates. We conclude that tertatolol, but not propranolol, increases GFR and PFR, and enhances urine output and sodium excretion in the isolated perfused rat kidney. These findings indicate that tertatolol preserves renal function by a mechanism independent of systemic changes.
Perico
N
N
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Remuzzi
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D013876:Thiophenes; D014563:Urodynamics / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D013876:Thiophenes; C005632:tertatolol