Browsing by Author "URETA, H"

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    DIURETIC EFFECT OF BREMAZOCINE, A KAPPA-OPIOID WITH CENTRAL AND PERIPHERAL SITES OF ACTION
    (1989) SALAS, SP; ROBLERO, J; URETA, H; HUIDOBROTORO, JP
    Intracerebroventricular or i.p. injections of bremazocine produced a dose-dependent diuretic response and increased glomerular filtration rate in hydrated as well as in nonhydrated rats. The potency and magnitude of the bremazocine-induced diuresis were more pronounced in the nonhydrated group of rats. That bremazocine has a central component of action is deduced from the fact that 0.1 .mu.g of the opioid administered centrally caused a significant increase in urine output; proportionally, larger doses of bremazocine were required to produce the same diuretic effect when the drug was administered parenterally. Bremazocine did not change the total amount of urinary Na+ and K+ as compared to the saline controls; it increased significantly the free water clearance. The bremazocine-induced diuresis was antagonized in a competitive fashion by 10 mg/kg of naloxone giving further support to the notion that the mechanism of action of bremazocine involves activation of kappa-opioid receptors. Bremazocine injected i.v. to nonanesthetized rats increased mean systemic blood pressure in a dose-dependent manner; the pressor action of the opiate was blocked and prevented by 1 mg/kg of naloxone. In contrast, i.c.v. administration of bremazocine did not change mean systemic blood pressure but produced a dose-related increase in urine output. To determine whether in addition to a central site bremazocine also activates a renal mechanism, experiments were performed in the isolated perfused rat kidney. Bremazocine (0.15-2.5 .mu.M) caused a dose-dependent diurectic response and a significant rise in the perfusion pressure as well as in glomerular filtration rate. In contrast to the whole animal studies, in vitro administration of bremazocine resulted in a marked natriuresis and kaliuresis proportional to the dose. The renal effects were antagonized by naloxone, suggesting the existence of a local opiate renal mechanism. In conclusion, the present results demonstrate that in addition to a central site of action, bremazocine activates renal mechanisms to regulate water and electrolytes metabolism. The complexity of the pharmacology of opiates in the regulation of urine output may be related to this dual mechanism.
  • No Thumbnail Available
    Item
    KAPPA-OPIATE-INDUCED DIURESIS AND CHANGES IN BLOOD-PRESSURE - DEMONSTRATION OF RECEPTOR STEREOSELECTIVITY USING (+)-TIFLUADOM AND (-)-TIFLUADOM
    (1987) URETA, H; LOPEZ, LF; PEREZ, A; HUIDOBROTORO, JP
    (+)-Tifluadom injected i.p. produced a biphasic response of urine output: within the first hour of its administration the drug produced antidiuresis followed by a diuretic phase. In contrast, the (-) isomer produced a modest reduction in urine output as compared to the output of the saline-treated rats. In addition, (+)-tifluadom markedly reduced the output of urinary Na+ and K+. The effects of (+)-tifluadom were blocked by 7.5 mg/kg naloxone but not by 10 mg/kg of the benzodiazepine antagonist Ro 15-1788. Parallel experiments demonstrated that the i.v. administration of (+)-tifluadom to non-anesthetized rats caused a dose-related pressor response that lasted for at least 15 min. This effect of (+)-tifluadom wa blocked and antagonized by naloxone. In contrast, (-)-tifluadom was either inactive on the cardiovascular system or produced short-lasting hypotension. In pentobarbital-anesthetized rats, 100 .mu.g/kg (+)-tifluadom caused a precipitous hypotension that was reversed by naloxone but not by Ro 15-1788.