Vasopressin in vasoplegic shock in surgical patients: systematic review and meta-analysis

Purpose: Vasoplegia, or vasoplegic shock, is a syndrome whose main characteristic is reducing blood pressure in the presence of a standard or high cardiac output. For the treatment, vasopressors are recommended, and the most used is norepinephrine. However, new drugs have been evaluated, and conflicting results exist in the literature. Methods: This is a systematic review of the literature with meta-analysis, written according to the recommendations of the PRISMA report. The SCOPUS, PubMed, and ScienceDirect databases were used to select the scientific articles included in the study. Searches were conducted in December 2022 using the terms "vasopressin," "norepinephrine," "vasoplegic shock," "postoperative," and "surgery." Meta-analysis was performed using Review Manager (RevMan) 5.4. The endpoint associated with the study was efficiency in treating vasoplegic shock and reduced risk of death. Results: In total, 2,090 articles were retrieved; after applying the inclusion and exclusion criteria, ten studies were selected to compose the present review. We found no significant difference when assessing the outcome mortality comparing vasopressin versus norepinephrine (odds ratio = 1.60; confidence interval 0.47-5.50), nor when comparing studies on vasopressin versus placebo. When we analyzed the length of hospital stay compared to the use of vasopressin and norepinephrine, we identified a shorter length of hospital stay in cases that used vasopressin; however, the meta-analysis did not demonstrate statistical significance. Conclusions: Considering the outcomes included in our study, it is worth noting that most studies showed that using vasopressin was safe and can be considered in managing postoperative vasoplegic shock.

Clinical characteristics of congenital nephrogenic diabetes insipidus / 中华内科杂志

The purpose of this study was to improve the ability to visualize and diagnose congenital nephrogenic diabetes insipidus (CNDI). The clinical manifestations, laboratory examination findings, imaging features and treatment outcomes of 22 patients with CNDI admitted to the First Affiliated Hospital of Zhengzhou University from May 2013 to May 2020 were retrospectively analyzed. Among the 22 patients with CNDI, 86.4% (19 cases) were male. The age of the 22 patients ranged from 2 months to 47 years old, in which 20 cases were younger than 30 years old and 2 cases were older than 30 years old. The clinical manifestations were polydipsia and polyuria, accompanied with various degrees of fever, defects in growth and development, and increased serum creatinine in some patients. Fifteen patients (68.2%) had different degrees of bilateral kidney and ureteral hydronephrosis, and increased residual urine volume in the bladder. Pituitary magnetic resonance imaging (MRI) enhanced scan showed that the high signal intensity in the posterior pituitary lobe was not detectable in 5 cases (22.7%), and blurred in 6 cases (27.3%). Seven tested patients were all found AVPR2 gene mutation. For patients with suspected CNDI, water-inhibiting vasopressin test and genetic testing should be performed in time so as to confirm diagnosis and treat as early as possible.

Analysis of influencing factors associated with responsiveness to terlipressin in septic shock patients / 中国基层医药

Objective@#To determine the relevant factors associated with the responsiveness of terlipressin in patients with septic shock.@*Methods@#From June 2013 to June 2018, the clinical data of patients with septic shock in the intensive care unit (ICU) of the Affiliated Hospital of Hangzhou Normal University who received catecholamine and treated with terlipressin for at least 6 h, were retrospectively analyzed.Then, the patients were categorized as either responders or non-responders according to their responsiveness to terlipressin.The potential associations between some clinical indicators before the addition of terlipressin and responsiveness to terlipressin were analyzed.@*Results@#A total of 132 patients with septic shock were included in this study, including 60cases(45.45%) responders and 72cases(54.54%) non-responders.Compared with responders, non-responders had significantly higher ICU mortality and hospital mortality (ICU mortality: 20.00% vs.72.22%, χ2=35.734, P<0.001; hospital mortality: 81.67% vs.94.44%, P=0.028) and higher median blood lactate (2.73 mmol/L vs.5.22 mmol/L, Z=3.181, P=0.001). Multivariate logistic regression analysis showed that blood lactate level before the addition of terlipressin was a risk factor for patients with no response to terlipressin (odds ratio 1.130, 95% confidence interval 1.05-1.23, P=0.002). Receiver operating characteristic curve showed that the area under the curve of blood lactate before the addition of terlipressin was 0.661.@*Conclusion@#Blood lactate levels may be useful in predicting terlipressin responsiveness in patients with septic shock.

Analysis of influencing factors associated with responsiveness to terlipressin in septic shock patients / 中国基层医药

Objective To determine the relevant factors associated with the responsiveness of terlipressin inpatients with septic shock.Methods From June 2013 to June 2018,the clinical data of patients with septic shock in the intensive care unit ( ICU) of the Affiliated Hospital of Hangzhou Normal University who received catecholamine and treated with terlipressin for at least 6 h,were retrospectively analyzed .Then,the patients were categorized as either responders or non -responders according to their responsiveness to terlipressin .The potential associations between some clinical indicators before the addition of terlipressin and responsiveness to terlipressin were analyzed .Results A total of 132 patients with septic shock were included in this study,including 60cases(45.45％) responders and 72cases(54.54％) non -responders.Compared with responders , non -responders had significantly higher ICU mortality and hospital mortality (ICU mortality:20.00％ vs.72.22％,χ2 =35.734,P<0.001;hospital mortality:81.67％vs.94.44％,P=0.028) and higher median blood lactate (2.73 mmol/L vs.5.22 mmol/L,Z=3.181,P=0.001).Multivariate logistic regression analysis showed that blood lactate level before the addition of terlipressin was a risk factor for patients with no response to terlipressin (odds ratio 1.130,95％confidence interval 1.05-1.23,P=0.002).Receiver operating characteristic curve showed that the area under the curve of blood lactate before the addition of terlipressin was 0.661.Conclusion Blood lactate levels may be useful in predicting terlipressin responsiveness in patients with septic shock .

Factors Associated with Postoperative Diabetes Insipidus after Pituitary Surgery

BACKGROUND: Determining risk factors for diabetes insipidus (DI) after pituitary surgery is important in improving patient care. Our objective is to determine the factors associated with DI after pituitary surgery. METHODS: We reviewed records of patients who underwent pituitary surgery from 2011 to 2015 at Philippine General Hospital. Patients with preoperative DI were excluded. Multiple logistic regression analysis was performed and a predictive model was generated. The discrimination abilities of the predictive model and individual variables were assessed using the receiving operator characteristic curve. RESULTS: A total of 230 patients were included. The rate of postoperative DI was 27.8%. Percent change in serum Na (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.15 to 1.69); preoperative serum Na (OR, 1.19; 95% CI, 1.02 to 1.40); and performance of craniotomy (OR, 5.48; 95% CI, 1.60 to 18.80) remained significantly associated with an increased incidence of postoperative DI, while percent change in urine specific gravity (USG) (OR, 0.53; 95% CI, 0.33 to 0.87) and meningioma on histopathology (OR, 0.05; 95% CI, 0.04 to 0.70) were significantly associated with a decreased incidence. The predictive model generated has good diagnostic accuracy in predicting postoperative DI with an area under curve of 0.83. CONCLUSION: Greater percent change in serum Na, preoperative serum Na, and performance of craniotomy significantly increased the likelihood of postoperative DI while percent change in USG and meningioma on histopathology were significantly associated with a decreased incidence. The predictive model can be used to generate a scoring system in estimating the risk of postoperative DI.

Anesthetic experience of frontotemporal dementia patient with severe autonomic dysfunction: a case report / 대한마취과학회지

Anesthetic experience in frontotemporal dementia (FTD) with severe hypotension associated autonomic dysfunction has not yet been reported. Here in case, we report on the case of treatment with vasopressin to refractory hypotension in FTD patient. A 54-year-old male presented with a ten-year history of FTD with frequent syncope. The patient was scheduled to undergo subtotal gastrectomy for resection of stomach cancer. During the operation, sudden hypotension occurred and it was refractory to fluid and 1 unit of blood resuscitation and did not respond to catecholamine. Transesophageal echocardiography showed normal heart with adequate volume state. After intravenous administration of arginine vasopressin, the patient's vital signs returned to baseline values. Arginine vasopressin might be considered as a valuable alternative for treatment of severe refractory hypotension in autonomic dysfunction patients with FTD.

Accuracy of vasopressin secretion in the late phase of septic shock for predicting patient outcomes / 中华麻醉学杂志

Objective To evaluate the accuracy of vasopressin (VP) secretion in the late phase of septic shock for predicting patient outcomes and further investigate its relationship with the prognosis of septic shock.Methods Fifty-five patients presented at late phase of septic shock,who were admitted to the intensive care unit of our hospital,were enrolled.Their VP secretion was measured.The method for measurement was as follows:3％ sodium chloride solution 600 ml was infused over 2 h,serum concentrations of VP and sodium were measured before and after infusion,the difference in VP before and after infusion (△VP) and in Na before and after infusion (△Na) was calculated,and △VP/△Na was used to reflect VP secretion.The patients were divided into either abnormal secretion of VP group (△ VP/△ Na ≤ 0.5 ng/mmol) or normal secretion of VP group (△VP/△Na＞0.5 ng/mmol) according to △VP/△Na ratio.Immediately before testing VP secretion,venous blood samples were collected for determination of serum lactic acid and C-reactive protein concentrations.The consumption of vasoactive drugs at the moment of enrollment and 28-day fatality rate were recorded.Results There were 30 cases in abnormal group (54％) and 25 cases in normal group (46％).Compared with normal group,the serum lactic acid,C-reactive protein concentrations and consumption of dopamine or norepinephrine were significantly increased,and the 28-day fatality rate was increased (67％ vs 40％) in abnormal group.ROC curve analysis showed that when △VP/△Na 0.5 ng/mmol was used as the criteria for determining prognosis,the sensitivity was 66.7％,specificity was 64.0％,and the area under the ROC curve was 0.828.Conclusion VP secretion in the late phase of septic shock may affect patient prognosis.

Relationship between perioperative changes in plasma arginine vasopressin and angiotensin Ⅱ and outcome in patients undergoing off-pump coronary artery bypass grafting / 中华麻醉学杂志

ObjectiveTo investigate the relatioaship between the changes in perioperative plasma vasopressin (VP) and angiotensin Ⅱ ( Ang Ⅱ ) concentrations and outcome in patients undergoing off-pump coronary attery bypass grafting (OPCABG).MethodsFifty ASA Ⅰ -Ⅲ patients (NYHA Ⅰ -Ⅲ ) of both sexes,aged 45-79yr,undergoing OPCABG,were enrolled in this study.Blood samples were collected before induction of anesthesia (T1,baseline),before skin incision (T2),at 10 and 30 min after skin incision (T3,T4 ),10 min after protamine injection (T5),end of operation (T6 ) and 24 h after operation (T7).Based on the intraoperative plasma VP concentrations,the patients were divided into high level group ( n =26) and low level group ( n =24) by hierarchical clustering analysis.The risk factors for perioperative lower plasma VP concentration were determined by logistic regression analysis.ResultsPlasma VP concentrations were significantly lower,while plasma Ang Ⅱ concentrations were significantly higher at T2-6 in the low level group than in the high level group.The incidence of vasoplegia (high cardiac output and low peripheral resistance) was significantly higher,the intra- and post-operative use of vasodilator was less,the tracheal extubation time,ICU stay and post-operative hospital stay were longer,and preoperative left ventricular ejection fraction (LVEF) was lower in low level group than in high level group.Logistic regression analysis showed that preoperative low LVEF was a risk factor for intraoperative low plasma VP concentration and OR was 1.122.Conclusion Plasma VP and Ang Ⅱ concentrations demonstrate an opposite trend of change during OPCABG.The incidence of vasoplegic syndrome is significantly higher and the outcome poor in low plasma VP group.Preoperative low LVEF is a risk factor for development of low plasma VP during OPCABG.

Cirugía cardiaca con circulación extracorpórea: síndrome vasoplégico y vasopresina / Vasoplegic syndrome and its treatment with vasopressin during cardiac surgery with cardiopulmonary bypass

Cardiac surgery with cardiopulmonary bypass is associated with systemic inflammatory response. In some cases this clinical condition is characterized by severe hypotension due to low systemic vascular resistance during and after cardiopulmonary bypass. Afew ofthese cases do not respond to volume or catecholamines. This condition is known as vasoplegic syndrome. Its etiology is notfully understood today and carries associated morbidity and mortality In this syndrome, vasopressin levéis are reduced, as in septic and hypovolemic shock. Supplementary vasopressin improves blood pressure and might be considered as an alternative treatment. Severa! reports have shown benefits when used alone or in combination with catecholamines. However, further studies are necessary to find the most appropriate use ofthe drug for vasoplegic syndrome.

Pathogenesis and New Treatment of Autosomal Dominant Polycystic Kidney Disease / 대한신장학회지

The discovery of the genes and their respective proteins that are associated with autosomal dominant polycystic kidney disease (ADPKD) has revolutionized the field of ADPKD biology. Recent studies indicate that the pathogenesis of ADPKD is linked to abnormalities in the primary cilium in the kidney. Inactivation of ciliary proteins in the postnatal kidney has uncovered novel roles of primary cilia in regulating tubular growth and repair after injury. Furthermore, defective tubular repair after injury may contribute to the progression of ADPKD. Studies of signaling pathways that are perturbed in ADPKD have identified potential targets for pharmacological therapy. Better understanding of the downstream consequences of ADPKD mutations has identified a number of therapeutic targets that are now being tested in preclinical and clinical trials. The author summarized recent insights in the pathogenesis of ADPKD including the genetics of ADPKD, the properties of the respective polycystin proteins, the role of cilia, some cell-signaling pathways and new therapeutic interventions.

Is There Escape from Renal Actions of Vasopressin in Rats with a Hyponatremia for Greater than 48 Hours?

Escape from the renal actions of vasopressin is said to occur in rats with chronic hyponatremia. Our objective was to provide specific evidence to test this hypothesis. Hence the osmolality in the excised renal papilla and in simultaneously voided urine (U(Osm)) was measured in rats with and without hyponatremia. To induce hyponatremia, rats were fed low-electrolyte chow for 6 days. In the first 3 days, water was provided ad lib. On days 4 to 6, a long acting vasopressin preparation (dDAVP) was given every 8 hours to induce water retention. The hyponatremic rats drank 21 mL 5% sucrose on day 4 and 6 mL on day 5. On the morning of day 6, these rats were given 10 mL of 5% glucose in water (D5W) by the intraperitoneal route at 09:00 hour and at 11:00 hour. Analyses were performed in blood, urine, and the excised renal papilla at 13:00 hour on day 6. The concentration of Na+ in plasma (P(Na)) in rats without intraperitoneal D5W was 140+/-1 mEq/L (n=7) whereas it was 112+/-3 mEq/L in the hyponatremic group (n=12). The hyponatremic rats had a higher osmolality in the excised papillary (1,915+/-117 mOsm/kg H2O) than the U(Osm) (1,528+/-176 mOsm/kg H2O, P<0.05). One explanation for this difference is that the rats escaped from the renal action of vasopressin. Nevertheless, based on a quantitative analysis, other possibilities will be considered.

Thiazide-Induced Hyponatremia

The importance of thiazide-induced hyponatremia (TIH) is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as first-line treatment of essential hypertension have been introduced. Thiazide diuretics act by inhibiting reabsorption of Na+ and Cl- from the distal convoluted tubule by blocking the thiazide-sensitive Na+/Cl- cotransporter. Thus, they inhibit electrolyte transport in the diluting segment and may impair urinary dilution in some vulnerable groups. Risk factors predisposing to TIH are old age, women, reduced body masses, and concurrent use of other medications that impair water excretion. While taking thiazides, the elderly may have a greater defect in water excretion after a water load compared with young subjects. Hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as reduction of renal function with aging, ingestion of other drugs that affect free water clearance, or changes in water or sodium intake. While some patients are volume depleted on presentation, most appear euvolemic. Notably serum levels of uric acid, creatinine and urea nitrogen are usually normal or low, suggestive of syndrome of inappropriate secretion of antidiuretic hormone. Despite numerous studies, the pathophysiological mechanisms underlying TIH are unclear. Although the traditional view is that diuretic-induced sodium or volume loss results in vasopressin-induced water retention, the following 3 main factors are implicated in TIH: stimulation of vasopressin secretion, reduced free-water clearance, and increased water intake. These factors will be discussed in this review.

Evaluation of kidney function in vasopressin-deficient rats by using dynumic enhanced MRI / 中华泌尿外科杂志

Objective To evaluate the renal function response to vasopressin in obstructed and non-obstructed kidney in vasopressin-deficient rats by using dynamic enhanced MRI. Methods This study included 26 vasopressin-deficient Brattleboro(BB)rats.Unilateral ureteral obstruction(UUO) model was set up in 12 BB rats.After releasing UU0 24 h,treatment of AVP was given in 7 non-obstrueted and 7 obstructed BB rats for 6 d.Seyen normal Wistar rats and 7 BB rats were used as control.Dynamic enhanced MRl was performed at 0-60 min following the administration of GadoliniumDTPA(0.05 mmol/kg)and the mean relative signal intensity(RSI)was measured. Results BB rats RSI increase occurred during the first minute,with a maximum mean RSI of(149±10)%in cortex,(155±13)%in medulla and(146±13)%in pelvis.Then,a gradual decrease in the cortical RSI occurred,after which a small increase was observed in Phase 3.BB rats RSI patterns were different from Wistar rats.After AVP treatment,mean RSI of BB rats in cortex,medulla and pelvis reached a maximum of(180±6)%,respectively at 30 sec,followed by a fast decrease at 1 min.Then,RSI decreased gradually.Phase 3 demonstrated a moderate increase in medullary and a relative large increase in pelvic RSI until 30 min after injection,after which RSI returned to baseline.BB rats RSI patterns after AVP treatment were similar to that of Wistar rats.Cortical,medullary and pelvic mean RSI increased slowly compared to non UUO rats.In phase 3,mean RSI of all segments decreased gradually.UUO rats RSI patterns were different from non UUO rats.After AVP treatment in UUO rats,mean RSIs of all segments increased faster compared to UUO rats without AVP.Cortical mean RSI reached a maximum of(193±7)% at 2 mim Mean RSI of medulla were unchanged,but the pelvic mean RSI deereased gradually to a minimum of(77±5)%at 5 min.Phase 3 was characterized by a slight recovcry of all RSIs.UUO rats RSIs were recovered after AVP treatment.The renal blood flow(RBF)of UUO rats was decreased to(1.1±0.1)m1·min-1·100g-1,wherease the RBF was increased to (1.9±O.3)ml·min-1·100g-1 after injecting AVP. Conclusion Dynamic enhanced MRI may provide useful information for distinguishing between kidneys having changes in the renal vasopressin concentration and the kidneys suffer from the obstructed renal damage.

Ubiquitination of Aquaporin: in the kidney

Ubiquitination is known to be important for endocytosis and lysosomal degradation of aquaporin-2 (AQP2). Ubiquitin (Ub) is covalently attached to the lysine residue of the substrate proteins and activation and attachment of Ub to a target protein is mediated by the action of three enzymes (i.e., E1, E2, and E3). In particular, E3 Ub-protein ligases are known to have substrate specificity. This minireview will discuss the ubiquitination of AQP2 and identification of potential E3 Ub-protein ligases for 1-deamino-8-D-arginine vasopressin (dDAVP)-dependent AQP2 regulation.

Fluorescence Quenching to Measure dDAVP-induced Cell Volume Changes in Kidney Collecting Duct Cell / 대한신장학회지

PURPOSE: Cell volume regulation is critical in kidney collecting duct cells which are subjected to large transepithelial osmotic gradients and stimulation of vasopressin. The present study aimed at validating the usefulness of the fluorescence quenching method to measure rapid changes in the cell volume of the kidney collecting duct cells in response to changes of extracellular osmolality and/or dDAVP (V2 receptor agonist) stimulation. METHODS: M-1 cell (a mouse cortical collecting duct cell line) was used and the data presented traces of cellular fluorescence in M-1 cells loaded with calcein collected over time as extracellular osmolality was repeatedly changed or dDAVP was treated. And the "initial relative rate of cell volume changes" was calculated. RESULTS: M-1 cells loaded with calcein revealed that fluorescence was increased when exposed to low extracellular osmolality (250 mOsm/KgH2O), whereas it was decreased by high extracellular osmolality (350 mOsm/KgH2O). This could reflect volume-dependent changes in fluorescence intensity in the range of quenching concentrations. The calculated "initial relative rate of cell volume changes" in M-1 cells during 1 sec was increased-7-fold by dDAVP treatment (10(-8)M, 2 min), compared with vehicle treatment when extracellular osmolality was changed from 350 to 250 mOsm/KgH2O. CONCLUSION: This study suggests that a fluorescence quenching method could be exploited for investigating an effect of dDAVP or other drugs/chemicals on the relative rate of cell volume changes in the kidney collecting duct cells.

Short-term Outcomes of the Combination of Vasopressin and Epinephrine versus Epinephrine Alone for Out-of-hospital Cardiac Arrest: A Prospective Observational Study

PURPOSE: A recent study demonstrated that the effects of vasopressin were superior to epinephrine in patients with asystole. According to the Korean national registry of out-ofhospital cardiac arrest (OHCA), more than 2/3 of paients had asystole. This study was performed to evaluate whether the combined administration of vasopressin and epinephrine in the emergency department (ED) for patients with OHCA would increase survival and survival discharge. METHODS: From October 2007 to June 2008, we changed the cardiopulmonary resuscitation (CPR) protocol in adult, non-traumatic OHCA in that 40 U of vasopressin was to be administered as soon as possible followed by epinephrine (VSP group). Data about cardiac arrest were collected using the Utstein templates. Data from January to September 2007, when vasopressin had not been used, were also collected for comparative analysis (EPN group). These two groups were compared in terms of rate of survival and survival discharge. RESULTS: There were 59 and 62 patients in the EPN group and the VSP group, respectively. There were no significant differences in the baseline characteristics including age, cardiac rhythm of asystole, witnessed arrest, and bystander CPR. Survival was similar between the EPN group and VSP group (46% vs 57%, p=0.240) as was survival discharge (20% vs 15%, p=0.398, respectively). CONCLUSION: The combination therapy of vasopressin and epinephrine during CPR for OHCA does not show any survival advantage over epinephrine alone.

Expression of aquaporin 2 in rat kidney under hypoxia at an altitude of 4600 m / 中华肾脏病杂志

Objective To investigate the change of aquaporin 2 (AQP2) mRNA and protein levels in renal collecting duct of SD rats after hypoxin caused by rising of the altitude to 4600 m. Methods Forty male SD rats were randomly divided into 4 groups (24 h, 48 h, 72 h and 1 week group), and 10 rats in Xining city were used as control group. All the 40 SD rats were transported to Kekexili Natural Reservation areas (4600 m) in Qinghai province. Rats of four experimental groups were sacrificed and renal tissue samples were harvested at different time point respectively, the control group rats were treated in Xining city (2260 m) as well. The concentration of plasma antidiuretic hormone (ADH) was measured by radioimmunity method. The expression of AQP2 mRNA and proteins was evaluated by real-time fluorescent quantitative-PCR, Western blot and immunofluorescence assay. Results The concentration of plasma ADH was decreased at 24 h and was only 28.5% of that of control group, reaching the lowest concentration at 48 h [(86.94±6.49) μg/L vs (302.5±310.48) μg/L], then it increased gradually and was similar to the control group at 7 d [(306.46±11.14) μg/L vs (302.53±10.48)μg/L, P＞ 0.05]. There were significant differences of the control group with 24 h, 48 h and 72 h groups, respectively[(302.53± 10.48) μg/L vs (142.46±10.57)μg/L, (86.94±6.49)μg/L, (169.65±11.15) μg/L respectively, P＜0.01]. The change of AQP2 gene expression level was consistent with the change of ADH. It was decreased at the begining when exposure to altitude and it reached its lowest level at 48 h. It was then returned to high level similarly to that of the control group at 7 d (0.09±0.01 vs 0.09± 0.008, P＞0.05 ). There were significant differences of the control group with 24 h, 48 h and 72 h group, respectively (0.09±0.008 vs 0.04±0.005, 0.03±0.002, 0.04±0.003 respectively, P＜0.01 ). Conclusions AQP2 expression in the renal collecting duct of SD rats is altered over the period exposed to altitude. It is decreased in the early hypoxia period, and is increased in later period. This change may be related to the intensity of hypoxia, which is mediated by a potential adaptation mechanisms against hypoxia caused by high altitude.

The Effects of Vasopressin and Desmopressin on the Contractile and Relaxation Responses of Rabbit Cavernosal Smooth Muscle / 대한비뇨기과학회지

PURPOSE: This study aimed to investigate the effects of vasopressin and desmopressin on the contractile and relaxative responses of rabbit cavernosal smooth muscle. MATERIALS AND METHODS: Isometric tension studies were conducted to investigate the effects of vasopressin(10(-14)-10(-8)M) and desmopressin(10(-14)- 10(-8)M) on the contraction and relaxation responses of rabbits cavernous muscle strips in an organ bath. The effects of pretreatment with phenylephrine(10(-5)M), L-NAME(10(-5)M) and indomethacin(10(-5)M) on the contraction and relaxation responses of the vasopressin and desmopressin were also investigated. The statistics were analyzed by Student's t-test and ANOVA. RESULTS: Vasopressin contracted the strips in a dose-dependent manner, while desmopressin did not. The phenylephrine-induced contraction was dose-dependently increased by vasopressin, but it was dose-dependently relaxed by desmopressin. L-NAME pre-treatment did not block the relaxation response, but indomethacin pre-treatment did. Vasopressin- induced contraction occurred the via V(1) receptor, while desmopressin- induced relaxation occurred via the V(2) receptor. CONCLUSIONS: Vasopressin, in pathophysiological circumstances, would worsen erectile dysfunction. On the contrary, desmopressin, which may induce an endothelium-dependent relaxation of the cavernous smooth muscles, would be good for erectile function.

Vasopressin and Vasopressin Receptor Antagonists

Vasopressin, a neurohypophyseal peptide hormone, is the endogenous agonist at V1a, V1b, and V2 receptors. The most important physiological function of vasopressin is the maintenance of water homeostasis through interaction with V2 receptors in the kidney. Vasopressin binds to V2 receptor and increases the number of aquaporin-2 at the apical plasma membrane of collecting duct principal cells. That induces high water permeability across the membrane. Several non-peptide vasopressin receptor antagonists have been developed and are being studied primarily for treating conditions characterized by hyponatremia and fluid overload. Further studies are needed to determine how they are best used in these situations.

Angiotensin II AT1 Receptor Blockade Changes Expression of Renal Sodium Transporters in Rats with Chronic Renal Failure

We aimed to examine the effects of angiotensin II AT1 receptor blocker on the expression of major renal sodium transporters and aquaporin-2 (AQP2) in rats with chronic renal failure (CRF). During 2 wks after 5/6 nephrectomy or sham operation, both CRF rats (n=10) and sham-operated control rats (n=7) received a fixed amount of low sodium diet and had free access to water. CRF rats (n=10) were divided into two groups which were either candesartan-treated (CRF-C, n=4) or vehicletreated (CRF-V, n=6). Both CRF-C and CRF-V demonstrated azotemia, decreased GFR, polyuria, and decreased urine osmolality compared with sham-operated rats. When compared with CRF-V, CRF-C was associated with significantly higher BUN levels and lower remnant kidney weight. Semiquantitative immunoblotting demonstrated decreased AQP2 expression in both CRF-C (54% of control levels) and CRF-V (57%), whereas BSC-1 expression was increased in both CRF groups. Particularly, CRF-C was associated with higher BSC-1 expression (611%) compared with CRF-V (289%). In contrast, the expression of NHE3 (25%) and TSC (27%) was decreased in CRF-C, whereas no changes were observed in CRF-V. In conclusion, 1) candesartan treatment in an early phase of CRF is associated with decreased renal hypertrophy and increased BUN level; 2) decreased AQP2 level in CRF is likely to play a role in the decreased urine concentration, and the downregulation is not altered in response to candesartan treatment; 3) candesartan treatment decreases NHE3 and TSC expression; and 4) an increase of BSC-1 is prominent in candesartan-treated CRF rats, which could be associated with the increased delivery of sodium and water to the thick ascending limb.