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Endocrinology and metabolism
Published in Kaji Sritharan, Jonathan Rohrer, Alexandra C Rankin, Sachi Sivananthan, Essential Notes for Medical and Surgical Finals, 2021
Kaji Sritharan, Jonathan Rohrer, Alexandra C Rankin, Sachi Sivananthan
Antidiuretic hormone (arginine vasopressin or AVP) and oxytocin are synthesised in the supraoptic and paraventricular nuclei of the hypothalamus and stored and then finally secreted from the posterior pituitary. AVP acts on V2 receptors on the basolateral membrane of the distal nephron leading to water conservation.
Cardiovascular, Hemodynamic, and Critical Care Considerations in the Patient With Necrotizing Enterocolitis
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Christine C. Pazandak, Zachary A. Vesoulis, Misty Good
Arginine vasopressin is a neuropeptide that regulates fluid homeostasis and vascular tone (15, 44). Vasopressin is released by the posterior pituitary in response to either decreased circulating volume or increased osmolarity (15). Vasoconstriction occurs when vasopressin binds to the V1 and V2 receptors located in the smooth muscle of the peripheral vasculature, and V2 receptors located in the kidney mediate fluid homeostasis (15, 46). Three retrospective studies evaluating vasopressin treatment in preterm infants with refractory hypotension found that vasopressin can significantly increase the MABP and decrease catecholamine dependence (46–48). Given these observations, a subsequent randomized controlled pilot study was conducted by Rios et al. to compare early vasopressin versus dopamine for the treatment of hypotension in ELBW infants (49). They found that both drugs improved MABP, and the infants who had received vasopressin had “lower mean PaCO2 levels, received fewer doses of surfactant and did not have tachycardia” compared to the infants who had received dopamine (49). In addition, Ni et al. explored the theoretical risks of oliguria or anuria, hyponatremia, lactic acidosis, and severe vasoconstriction and discovered that these did not occur in the very low-birth-weight (VLBW) infants (48). All of these findings are promising, but due to small sample sizes, a larger phase 2 or phase 3 clinical trial is necessary before this can be broadly applied to clinical practice.
The Hypothalamic-Pituitary-Adrenal Axis in Functional Somatic Illness
Published in Peter Manu, The Psychopathology of Functional Somatic Syndromes, 2020
The experiment was carried out after an all-night fast. Four blood samples were drawn at 15-minute intervals to establish the baseline concentration of vasopressin, cortisol, and adrenocorticotropin hormone. The procedure continued with an arginine vasopressin (aqueous pitressin) intravenous infusion at a dose of 1 mIU/kg/minute over one hour. Blood was sampled at 15-minute intervals during the infusion and for one hour afterward. Additional data were collected with questionnaires assessing mood states, arousal levels, and functional well-being.
Vasopressin receptor antagonists: a patent summary (2018-2022)
Published in Expert Opinion on Therapeutic Patents, 2023
Ferenc Baska, Éva Bozó, Tamás Patócs
Researchers at the Xuzhou Medical University discovered new benzodiazepine derivatives as novel V2 receptor antagonists for the treatment of autosomal dominant kidney disease [72]. In 2022 they published benzazepine compounds (31, Figure 8) as a potential treatment or prevention of disorders including hypertension, dysmenorrhea, adrenal hyperplasia, chronic congestive heart failure, liver cirrhosis, depression, hyponatremia, or PKD [73]. An in vivo test was performed to determine the antagonistic effect of compounds on arginine vasopressin receptors by inhibiting the action of cAMP using PKD1 knockout mice. Results revealed that these compounds significantly delayed the occurrence and development of PKD compared with tolvaptan and control. In another patent application, benzodiazepine pyrrole compounds (32, Figure 8) are described by Xuzhou Medical University [74]. The compounds are arginine vasopressin V2 receptor antagonists that can be used as pharmacological tools in studying the kinetics of receptor-ligand binding.
Physiological characterization of an arginine vasopressin rat model of preeclampsia
Published in Systems Biology in Reproductive Medicine, 2022
Sapna Ramdin, Thajasvarie Naicker, Virushka Pillay, Sanil D. Singh, Sooraj Baijnath, Blessing N Mkhwanazi, Nalini Govender
Earlier studies also linked AVP to arterial blood pressure regulation (Jablonskis and Howe 1993; Song and Martin 2006; Li et al. 2012). The elevations in both systolic and diastolic blood pressure in our study throughout pregnancy in the PAVP group, suggests that arginine vasopressin stimulates the renin-angiotensin aldosterone system (RAAS). This results in vasoconstriction, which is mediated via the V1a receptor and consequently increases peripheral resistance and systemic blood pressure as observed in our study (Qian 2018). Myocardial atrial contraction results in an atrial-induced increase in end-diastolic pressure, which subsequently enhances ventricular contraction. Arginine vasopressin increases the impact of norepinephrine and Ang II on cardiac muscle and blood vessels thus altering hemodynamic function (Lee et al. 2003), and negatively affects myocardial contraction (Goldsmith 2005; Goldsmith and Gheorghiade 2005). Chronic hypertension results in diastolic dysfunction and consequent left ventricular hypertrophy thereby reducing cardiac compliance (Lorell and Carabello 2000). This results in a higher diastolic pressure–volume relationship where even minor elevations in left ventricular end-diastolic volume induces a significant rise in left ventricular end diastolic pressure (Gutierrez and Blanchard 2004). The pronounced effect of AVP on diastolic pressure may be due to the exaggerated interaction of AVP with the V1A and V2 receptors on peripheral blood vessels (Goldsmith 2005; Goldsmith and Gheorghiade 2005).
Recent advances in proteolytic stability for peptide, protein, and antibody drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Xianyin Lai, Jason Tang, Mohamed E.H. ElSayed
The small intestine is another major part of the human digestive system and further processes macromolecules into tri-, di-, and mono-peptides [38]. In small intestinal fluids, proteins showed greater stability than peptides. The reason might be that proteins have more complex secondary and tertiary structures, leading to less easily accessible peptide bonds [40]. Therefore, peptides were more often evaluated in small intestinal fluids than proteins were. Oxytocin and vasopressin are pituitary neuropeptides, functioning as an integrated, adaptive system, allowing the mammalian body to survive, maintain homeostasis, and reproduce [41]. The two molecules are potential drugs to treat social deficits in neurodevelopmental disorders, including autism spectrum disorder [42]. A modified vasopressin, 1- deamino-8-D-arginine-vasopressin (dDAVP), has been successfully intranasally used in patients with central diabetes insipidus. Buccal administration of oxytocin in pregnant women at term is followed by uterine contractions and increased plasma concentrations of oxytocin. However, their oral bioavailability was only 0.1–0.2% in healthy volunteers. Arginine-vasopressin, oxytocin, and their synthetic analogues were incubated in human small intestinal fluid from healthy volunteers. The quantification of degradation was carried out by reversed-phase high performance liquid chromatography (RP-HPLC). Arginine-vasopressin was completely degraded in 30 min, while dDAVP remained 50% of the intact after 35 min. Oxytocin showed much more stability than dDAVP and arginine-vasopressin [43].