Vasopressin and septic shock

Septic shock continues to be one of the leading causes of death in the Intensive Care Units. When the shock state persists after adequate fluid resuscitation, vasopressor therapy is required to improve and maintain adequate tissue/organ perfusion in an attempt to improve survival and prevent the development of multiple organ dysfunction and failure. Various studies have suggested that exogenous administration of arginine vasopressin may be an effective adjunctive therapy to traditional catecholamines for the management of hypotension during septic shock. Vasopressin is both a vasopressor and an antidiuretic hormone. It also has hemostatic, gastrointestinal and thermoregulatory effects, and is an adrenocorticotropic hormone secretagogue. Vasopressin is released from the axonal terminals of magnocellular neurons in the hypothalamus. Vasopressin mediates vasoconstriction via VI-receptor activation on vascular smooth muscle and mediates its antidiuretic effect via V2-receptor activation in the renal collecting duct system. Vasopressin infusion of 0.01 to 0.04 U/min in patients with septic shock increases plasma vasopressin levels. Current guidelines from the Surviving Sepsis Campaign recommend arginine vasopressin 0.03 unit/minute may be added to norepinephrine with the anticipation of an effect equal to higher doses of norepinephrine alone. Clinicians must be knowledgeable about the use of vasopressin in septic shock, including controversial areas where guidelines do not always provide solid recommendations

Evaluation of vasopressin mediated effects on hemostatic mechanisms: relationship with aquaporins and caveolin proteins.

With a view to evaluate the role of AQP-1 and caveolin proteins in the hemostatic actions of vasopressin, hemostasis was evaluated by bleeding and clotting time respectively.Groups of mice and guinea pigs were treated with arginine vasopressin (AVP) and 1-deamino-8D-AVP (DDAVP) to evaluate their effects on the hemostasis. DDAVP and AVP were able to appreciably reduce the bleeding and clotting time after sodium thiopentone, but not effectively after TEA treatment. Animal groups were pretreated with aquaporin-1 (AQP-1) blockers or water deprived to enhance the expression of AQP-1 water channels. Another group of animals were treated with caveolin protein modulators, cholera toxin (CTX) and the effect of vasopressin analogues evaluated. The results suggest that AQP-1 water channels and caveolin proteins contribute to modulate the hemostatic mechanisms of vasopressin.

Blood flow measurements in rats using four color microspheres during blockade of different vasopressor systems

The use of colored microspheres to adequately evaluate blood flow changes under different circumstances in the same rat has been validated with a maximum of three different colors due to methodological limitations. The aim of the present study was to validate the use of four different colors measuring four repeated blood flow changes in the same rat to assess the role of vasopressor systems in controlling arterial pressure (AP). Red (150,000), white (200,000), yellow (150,000), and blue (200,000) colored microspheres were infused into the left ventricle of 6 male Wistar rats 1) at rest and 2) after vasopressin (aAVP, 10 æg/kg, iv), 3) renin-angiotensin (losartan, 10 mg/kg, iv), and 4) sympathetic system blockade (hexamethonium, 20 mg/kg, iv) to determine blood flow changes. AP was recorded and processed with a data acquisition system (1-kHz sampling frequency). Blood flow changes were quantified by spectrophotometry absorption peaks for colored microsphere components in the tissues evaluated. Administration of aAVP and losartan slightly reduced the AP (-5.7 ± 0.5 and -7.8 ± 1.2 mmHg, respectively), while hexamethonium induced a 52 ± 3 mmHg fall in AP. The aAVP injection increased blood flow in lungs (78 percent), liver (117 percent) and skeletal muscle (>150 percent), while losartan administration enhanced blood flow in heart (126 percent), lungs (100 percent), kidneys (80 percent), and gastrocnemius (75 percent) and soleus (94 percent) muscles. Hexamethonium administration reduced only kidney blood flow (50 percent). In conclusion, four types of colored microspheres can be used to perform four repeated blood flow measurements in the same rat detecting small alterations such as changes in tissues with low blood flow.

Efeito da vasopressina em artérias coronárias epicárdicas caninas. Experimentos sobre a produção de óxido nítrico mediante a estimulação de receptores V1 / Effect of arginine vasopressin on the canine epicardial coronary artery. Experiments on V1-receptor-mediated production of nitric oxide

OBJECTIVE: To determine whether arginine vasopressin releases endothelium-derived nitric oxide (EDNO) from the epicardial coronary artery. METHODS: We studied segments of canine left circumflex coronary arteries suspended in organ chambers to measure isometric force. The coronary artery segments were contracted with prostaglandin F2alpha (2 x 10-6M) and exposed to a unique, strong arginine vasopressin concentration (10-6M) or titrated concentrations (10-9 a 10-5 M). RESULTS: The unique dose of arginine vasopressin concentration (10-6M) induced transient, but significant (p<0.05), relaxation in arterial segments with endothelium, and an increase, not significant, in tension in arteries without endothelium. Endothelium-dependent relaxation to arginine vasopressin was inhibited by Ng-monomethyl-L-arginine (L-NMMA, 10-5M) or N G-nitro-L-arginine (L-NOARG) (10-4M), 2 inhibitors of nitric oxide synthesis from L-arginine. Exogenous L-arginine (10-4M), but not D-arginine (10-4M), reversed the inhibitory effect of L-NMMA on vasopressin-mediated vasorelaxation. Endothelium dependent relaxation to vasopressin was also reversibly inhibited by the vasopressin V1-receptor blocker d(CH2)5Try(Me) arginine vasopressin (10-6M) (n=6, P<0.05). CONCLUSION: Vasopressin acts through V1 endothelial receptors to stimulate nitric oxide release from L-arginine

study on the effect of arginine vasopressin[AVP] on coronary flow

The effect of Arginine Vasopressin [AVP] on coronary flow was studied in the isolated heart of adult male rabbits. Five doses of the hormone [10-25-50-100-500 pg/ml] were used to study their effects on the coronary flow. One group of experiments [n = 5] were administrated a constant infusion of AVP in a dose of 100 pg/ml for 5 minutes, after which Creatin-Phospho-kinase enzyme [CPK] release from the cardiac muscle was estimated. The results showed that there is a significant reduction in coronary flow with the use of the large two doses [100 and 500 pg/ml]. A significant dose-dependent depression of coronary flow was also observed [r = + 0.92]. Moreover, the results showed a significant increase [+ 80.29%] in the CPK release-from the hearts infused with AVP continuously for five minutes. The data obtained medicate that AVP is a potent coronary constrictor in high doses only and produces myocardial damage. It was also found that the cyclooxygenase inhibitor [Ketoprofen] in the dose used [20 ug/ml] did not alter the direct AVP coronary constrictor response

Influence of calcium removal from bath solution on isolated rat duodenum contractions.

In this study whether extracellular Ca++ is essential to produce an increase of tension of isolated rat duodenum by ACh, 5-HT, AVP and KCl-, was examined. KCl- and AVP-evoked contractions were almost totally prevented by Ca++ removal from bath solution. The increase of tension of isolated duodenum caused by ACh or 5-HT was totally prevented after adding nifedipine, a Ca++ channel blocker, into Ca free solution. Our results suggest that ACh or 5-HT utilizes intracellular as well as extracellular sources of Ca++ to produce contraction in rat duodenum, whereas AVP-or KCl evoked contraction was mainly due to influx of Ca from extracellular sources.

Treatment of eneuresis in children with desmopressin [DDAVP]

The effectiveness of internasal instillation of the vasopressin analogue desmopressin [DDAVP] on the management of nocturnal enuresis was evaluated. Seventy-five children with primary enuresis were treated with desmopressin and thirty children were treated by placebo [same administration route using normal saline] serving as controls. The drug proved to be safe, more effective in older children and children who did not have enuresis every night. High doses [20 meg] gave better results than small doses [10 meg]

Mecanismos de acción de angiotensina II sobre la liberación de ACTH / Mechanism of action of angiotensin II in ACTH liberation

El presente trabajo fue desarrollado, utilizando sistemas in vitro e in vivo con el objeto de comparar la actividad liberadora de ACTH (ALC) de angiotensina II (A II) con la respectiva de otros péptidos neurales con ALC intrínseca, tales como el factor liberador de ACTH (CRF), arginina-vasopresina (AVP) y ocitocina (OXY), y determinar el sitio más probable de acción de A II para inducir liberación de ACTH. Inyecciones intraperitoneales de A II en ratas macho intactas aumentaron los niveles circulantes de ACTH, aunque dicha respuesta no fue tan pronunciada como las que produjeron menores dosis molares de CRF y AVP. La inyección intravenosa (i.v.) de A II en ratas macho centralmente bloqueadas no modificó los valores plasmáticos de ACTH, cuando CRF y AVP aumentó varias veces los valores de esta hormona. Además, las inyecciones i.v. de A II en ratas hembra deficientes de AVP (Brattleboro, D.I.) indujeron respuestas semejantes a las obtenidas en ratas hembras controles (Long Evans, L. E. y Sprague-Dawley, S-D), donde se incrementaron significativamente los valores de ACTH plasmática. Las ratas D.I. hiper respondieron a la inyección i.v. de CRF si se compara con la respuesta obtenida en las ratas control apropiadas (L.E.). Los estudios in vitro sugieren que A II es capaz de liberar ACTH de células adenohipofisarias dispersas obtenidas de donantes machos adultos en el rango 10**8 a 10**6 M. OXY fue capaz de liberar ACTH a la concentración 10**8 M. Las curvas respuesta-dependientes de la concentr

Effect of ADH on the toad efferent ducts

La ADH produce la reabsorción de fluidos en el aparato renal y en el tracto reproductor masculino de los mamíferos. Los conductos eferentes tienen origen mesonéfrico y están relacionados con ambos sistemas. Se estudió el efecto de la ADH, sobre los conductos eferentes del sapo y los cambios ultraestructurales. Las áreas citoplásmicas y nucleares de las células epiteliales aumentaron. Los núcleos se hicieron más claros, con disminución de la heterocromatina y profundos pliegues de sus envolturas. Es evidente un aumento del número de vesículas citoplásmicas, muchas de las cuales se abren a los espacios intercelulares y están asociadas con microfilamentos y microtúbulos. Estos hallazgos podrían indicar un aumento en el transporte de agua y sodio. Existe un probable efecto directo de la ADH en los conductos eferentes del sapo