The pressor effect of angiotensin-(1-7) in the rat rostral ventrolateral medulla involves multiple peripheral mechanisms

OBJECTIVE: In the present study, the peripheral mechanism that mediates the pressor effect of angiotensin-(1-7) in the rostral ventrolateral medulla was investigated. METHOD: Angiotensin-(1-7) (25 pmol) was bilaterally microinjected in the rostral ventrolateral medulla near the ventral surface in urethane-anesthetized male Wistar rats that were untreated or treated (intravenously) with effective doses of selective autonomic receptor antagonists (atenolol, prazosin, methyl-atropine, and hexamethonium) or a vasopressin V1 receptor antagonist [d(CH2)5 -Tyr(Me)-AVP] given alone or in combination. RESULTS: Unexpectedly, the pressor response produced by angiotensin-(1-7) (16 ± 2 mmHg, n = 12), which was not associated with significant changes in heart rate, was not significantly altered by peripheral treatment with prazosin, the vasopressin V1 receptor antagonist, hexamethonium or methyl-atropine. Similar results were obtained in experiments that tested the association of prazosin and atenolol; methyl-atropine and the vasopressin V1 antagonist or methyl-atropine and prazosin. Peripheral treatment with the combination of prazosin, atenolol and the vasopressin V1 antagonist abolished the pressor effect of glutamate; however, this treatment produced only a small decrease in the pressor effect of angiotensin-(1-7) at the rostral ventrolateral medulla. The combination of hexamethonium with the vasopressin V1 receptor antagonist or the combination of prazosin, atenolol, the vasopressin V1 receptor antagonist and methyl-atropine was effective in blocking the effect of angiotensin-(1-7) at the rostral ventrolateral medulla. CONCLUSION: These results indicate that angiotensin-(1-7) triggers a complex pressor response at the rostral ventrolateral medulla that involves an increase in sympathetic tonus, release of vasopressin and possibly the inhibition of a vasodilatory mechanism.

Manejo de ascitis refractaria e hiponatremia dilucional en pacientes con cirrosis / Management of refractory ascites and dilutional hyponatremia in cirrhotic patient

Ascites and dilutional hyponatremia are frequent conditions in cirrhotic patients and its occurrence has a worse prognosis. Thus, patients with ascites should generally be considered for referral for liver transplantation. The present article explores issues related with ascites classification and the treatment corresponding to each of the 3 degrees of ascites. Regarding refractory ascites, recommendations are included on the use of diuretics, large volume paracentesis with the administration of intravenous albumin and use of transjugular intrahepatic portosystemic shunt (TIPS). Finally, physiopathological aspects involved in the development of dilutional hyponatremia and vaptans treatment, are presented, which are aquaretics that selectively blockade vasopressin V2 receptors in the principal cells of the collecting ducts, being one of the most innovative pharmacological interventions for the management of hyponatremia in cirrhotic patients, in the recent years.

La ascitis e hiponatremia dilucional son complicaciones frecuentes en pacientes con cirrosis avanzada y su aparición implica un peor pronóstico. Por ello, los pacientes con ascitis deberían ser referidos para trasplante hepático. El presente artículo explora los aspectos relacionados con la clasificación de la ascitis y el tratamiento correspondiente a cada uno de los 3 grados de ascitis. En relación al manejo de la ascitis refractaria, se incluyen recomendaciones respecto a la eficacia del uso de diuréticos, paracentesis evacuadora radical con reposición de albúmina intravenosa y uso de cortocircuito porto-sistémico intrahepático (TIPS). Finalmente, se abordan los aspectos fisiopatológicos involucrados en el desarrollo de hiponatremia dilucional y el tratamiento con vaptanes, que son acuaréticos que bloquean selectivamente los receptores V2 de vasopresina en las células principales del túbulo colector, constituyendo una de las intervenciones farmacológicas más innovadoras en el manejo de la hiponatremia en cirrosis en los últimos años.

Hyponatremia and hypernatremia: disorders of water balance.

Total body water and tonicity is tightly regulated by renal action of antidiuretic hormone (ADH), reninangiotensin-aldosterone system, norepinephrine and by the thirst mechanism. Abnormalities in water balance are manifested as sodium disturbances--hyponatremia and hypernatremia. Hyponatremia ([Na+ < 136 meq/ l]) is a common abnormality in hospitalized patients and is associated with increased morbidity and mortality. A common cause of hyponatremia is impaired renal water excretion either due to low extracellular fluid volume or inappropriate secretion of ADH. Clinical assessment of total body water and urine studies help in determining cause and guiding treatment of hyponatremia. Acute and severe hyponatremia cause neurological symptoms necessitating rapid correction with hypertonic saline. Careful administration and monitoring of serum [Na+] is required to avoid overcorrection and complication of osmotic demyelination. Vasopressin receptor antagonists are being evaluated in management of euvolemic and hypervolemic hyponatremia. Hypematremia ([Na+] > 145 meq/l) is caused by primary water deficit (with or without Na+ loss) and commonly occurs from inadequate access to water or impaired thirst mechanism. Assessment of the clinical circumstances and urine studies help determine the etiology, while management of hypernatremia involves fluid resuscitation and avoiding neurological complications from hypernatremia or its correction. Frequent monitoring of [Na+] is of paramount importance in the treatment of sodium disorders that overcomes the limitations of prediction equations.

Efeito do bloqueio do hormônio antidiurético na natriurese associada à hemorragia intracerebroventricular experimental em ratos / Vasopressin V2 receptor antagonist effects in natriuresis after experimental intracerebroventricular hemorrage in rats

A hiponatremia é uma condição grave associada às lesões neurológicas, notadamente aos sangramentos no sistema nervoso central. Duas teorias têm sido apontadas como causadoras desta condição: a síndrome cerebral perdedora de sal e a síndrome da secreção inapropriada do hormônio antidiurético (HAD). Utilizou-se um bloqueador seletivo do receptor V2 renal do hormônio antidiurético em um modelo de sangramento intracerebroventricular...

Vasopressin mediates neuroprotection in mice by stimulation of V1 vasopressin receptors: influence of PI-3 kinase and gap junction inhibitors.

Neuroprotective effect of vasopressin analogues, arginine Vasopressin (AVP) and lysine Vasopressin (LVP) was evaluated against MgCl2 induced cerebral ischemia model. AVP significantly prevented (P < 0.01) MgCl2 (1M) induced cerebral ischemia as compared to lysine Vasopressin (LVP) which was less effective (P < 0.05). Pretreatment with PI-3 kinase inhibitors, Wortmannin and LY-294002 (50 microg/kg, ip) significantly attenuated the protective effects of vasopressin. AVP was also effective in reducing the maximal electroshock (MES) induced convulsive time and this protective effect was blocked by PI-3 kinase inhibitors. On the other hand, pretreatment with gap junction intracellular communication (GJIC) blocker, mephenamic acid (30 mg/kg, ip) significantly potentiated the MgCl2 induced cerebral ischemia. This enhancement of cerebral ischemia was not reversed by vasopressin analogue, LVP. The role of V1 vasopressin receptor was evaluated by pretreating the animals with non-selective V1 receptor antagonist, des Gly-NH2, d (CH2)5 [D-Tyr2, Thr4] OVT which reversed the effects of AVP suggesting a role for vasopressin V1 receptors. This study suggests that neurohypophyseal hormone, AVP is neuroprotective against MgCl2 induced cerebral ischemia and this effect is modulated by PI-3 kinase enzyme inhibitors and protein kinase C inhibitors through possible influence on the cerebral vascular tone. This study suggests that gap junctions have potential role in the induction of MgCl2 induced cerebral ischemia.