The role of AVP controlling the mean arterial blood pressure (MBP) in basal conditions remains unclear. We described that neurointermediate pituitary lobectomy (NIL) in rats, induced an early but transient diabetes insipidus and low MBP (8 weeks after lobectomy). To elucidate the chronological effects of NIL, we evaluated the AVP serum levels, water intake and urine output (diabetes insipidus, DI), and MBP immediately (0 to 6 hours post NIL) and 3, 15, 45 and 90 days post NIL. The renin, angiotensin II and aldosterone system (RAAS) was assessed at 3 and 45 days post NIL. Values were compared with the respective SHAM operated groups. Results: NIL caused significant and permanent AVP serum level decrease (10.6 ± 0.8 vs 2.4 ± 0.16 pg/ml (SD), SHAM vs NIL), transient DI (15‐30 days of duration) and permanent decrease of the MBP in 70% of the NIL animals (106.8 ± 3.15 vs 73.8 ± 3.2 mmHg). Hypotension was apparent 20‐30 minutes after NIL. No significant differences in the RAAS were evident.ConclusionsWe propose that in non‐stressed animals, basal serum levels of AVP are required to maintain the hydro‐electrolytic balance and MBP. Further studies are needed to explain why some animals did not develop hypotension, and to determine how cardiovascular, renal and hormone adaptive mechanisms in the NIL group support their survival.Supported by UAA‐PIFF and CONACYT, México and the Jarislowsky and L. Carr‐Harris Foundations

Liver fibrosis is due to the over deposition of collagens on the extracellular matrix, causing fibrotic septa and liver failure. Portocaval anastomosis (PCA) is a model of liver disease. Fibrogenesis is stimulated by AVP. We have described the healthy effect of the AVP deficiency, induced by neurointermediate pituitary lobectomy (NIL), on liver functions and cirrhosis. We hypothesize that blocking the AVP receptors with the V1a‐V2 AVP receptor antagonist conivaptan (CV) will induce the same healthy effects of NIL on liver fibrosis. Male Wistar rats were divided in 6 groups (8‐10 each): Sham surgery (SHAM), PCA, NIL, PCA+NIL, CV and PCA+CV. SHAM, NIL and the 4 groups with PCA were operated at week 0, whereas NIL surgery in the PCA+NIL group was done at week 8. CV treatments (30 mg/day/im/8 weeks) in the CV group started at week 0, whereas in the PCA+CV group started at week 8. NIL and CV groups were sacrificed at week 8, whereas SHAM, PCA, PCA+NIL and PCA+CV groups were sacrificed at week 16. At sacrifice, serum levels of ALT, AST, bilirubin, NH4, urea, albumin and glucose were assessed. Livers were weighed and samples were processed for glycogen content and the other processed for light microscopy analysis (slide tissues stained with H‐E, Masson and Sirius red). Results are summarized in Table 1. Effects of Vasopressin (AVP) Deficiency and Conivaptan (an AVP Receptors Antagonist) on Liver Physiology and Fibrosis in Rats with Protracted Portacaval Anastomosis GROUPS SHAM PCA NIL PCA+NIL CV PCA+CV (Basal values)Body weight=↓ (‐29%)↓ (‐22%)(‐ ↓(‐29%)=↓ (23%)(g)NS vs SHAMNS vs SHAMNS vs SHAMNS vs SHAMLiver weight=↓ (‐54%)===↓ (‐22%)(g)p<0.05 vsSHAMNS vsSHAMALT(U/L)=↑↑↑↑↑↑===AST(U/L)=↑↑↑↑↑↑↑↑==Total bilirubin (mg/dL)=↑↑↑====Unconjugated bilirubin (mg/dL)=↑↑↑====Albumin(g/dL)======Glucose (mg/dL)=====↓↓↓NH4(µg/dL)=↑↑↑===↑↑↑Urea(mg/dL)=↓↓↓====Liver glycogen(mg/gr of tissue)=↓↓↓==== Liver histopathology. In the PCA group, mainly in the periportal areas, small inflammatory infiltrates and big deposits of collagen were developed. Compared with the PCA, PCA+NIL and PCA+CV groups showed less inflammatory areas and much less collagen deposits. Conclusions, all results showed that: 1) AVP deficiency restores to normality the liver physiology and histology in the protracted liver disease, 2) Except the alterations in glycemia and NH4 metabolism, similar restored effects in liver histophysiology were induced by CV, suggesting that similar cellular mechanisms are involved, 3) Results strongly support that AVP is an important role in the pathophysiology of the liver fibrosis and possibly other fibrotic diseases.

It is known that arginine vasopressin (AVP) participate in the regulation of the immune responses, including the scarring. However, the effect of how AVP regulates this process is not clear. Here we describe the impact of AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) or blocking the V1a‐V2 AVP receptors with conivaptan (CON) on the kidney fibrosis (KF), induced by unilateral ureteral ligature (UUL). Groups of 5 Wistar male rats were prepared: Control Intact (CI), UUL, NIL, NIL+UUL, UUL+NIL and UUL+CON. The NIL group was operated 6 weeks before sacrifice. In the NIL+UUL group NIL was performed 3 weeks before UUL and sacrificed 3 weeks after. In the UUL+CON (3mg/kg/day/SC/3 weeks before sacrifice) the UUL was done 6 weeks before sacrifice. KF was evaluated in histological slides stained with H‐E, Masson and Sirius red. Results showed that UUL induced hydronephrosis, severe kidney fibrosis and loss of histological architecture, whose severity was related to each experimental condition: In the UUL severe fibrosis occurred in the ilium, pelvis, periglomerular, intraglomerular, intraluminal tubules and interstitial kidney areas. In comparison with the CI, NIL group showed normal kidney histology, whereas that, in comparison with the UUL the NIL+UUL group developed significant less histological alterations and less kidney fibrosis. In the UUL+NIL group (NIL surgery performed 3 weeks after UUL and sacrificed 3 weeks later), although histological changes and fibrosis were apparent, these were significantly less severe as compared with the UUL group. In comparison with the NIL+UUL group, the UUL+CON animals developed less severe fibrosis and less histopathological changes. Conclusions. Results showed that kidney fibrosis may be controlled by AVP deficiency or blocking the V1a‐V2 AVP receptors (CON) indicating a major role of AVP on the fibrotic process. Results also suggests that conivaptan may be used for kidney fibrosis treatment. Support or Funding Information Universidad Autónoma de Aguascalientes PIFF14‐1 and CONACYT 221262. México

Immune and vascular endothelial cells possess arginine vasopressin (AVP) receptors. AVP is an important stimulating/regulatory hormone in acquired immunity, whereas its role on innate immunity (INIM) is not well known. Neurointermediate pituitary lobectomy (NIL) in the rat causes permanent low AVP serum levels. Here, we investigate the AVP and INIM relationship in NIL rats (3 weeks after surgeries) subject to INIM tests: Phagocytic index (PI) (peritoneal macrophages (Mθ) erytrophagocytosis), and Skin Evans blue extravasation‐histamine doses‐response test. In the Study 1, NIL group was compared against Intact control (IC), sham operated (SHAM) and anterior pituitary lobectomysed (AL) groups. In the study 2, NIL group was compared against IC, NIL+desmopressin (a synthetic analog of AVP) and IC+conivaptan (antagonist of V1a‐V2 AVP receptors) groups. Results: Study 1 showed that as compared with the IC and AL groups, PI was significant decreased in NIL animals. In the Evans blue extravasation‐histamine test study, a significant and similar increases of skin edema histamine doses‐dependent occurred in NIL and IC+conivaptan groups, whereas no significant differences in IC and NIL+desmopressin groups were appreciated.ConclusionAVP plays an important role in phagocytic activity of the peritoneal Mθ and for the stabilization of the vascular endothelial cells permeability during histamine inflammation.Supported by UAA‐PIFF 14‐1. Universidad Autónoma de Aguascalientes, México and the Jarislowsky and Lloyd Carr‐Harris Foundations.