The carotid body has emerged as a therapeutic target for cardio-respiratory-metabolic diseases. With the expansive functions of the chemoreflex, we sought mechanisms to explain differential control of individual responses. We purport a remarkable correlation between phenotype of a chemosensory unit (glomus cell-sensory afferent) with a distinct component of the reflex response. This logic could permit differential modulation of distinct chemoreflex responses, a strategy ideal for therapeutic exploitation.
Vasopressin (AVP) and its receptors play a pivotal role in maintaining body homeostasis under physiological and pathophysiological conditions. As a consequence, the vasopressin system has emerged as an important target for both diagnostic and therapeutic applications in a number of medical conditions. Stoichiometric generation of AVP with copeptin, which is relatively accessible in the blood for measurements, makes copeptin a valuable surrogate of AVP. In this review, we present the regulation of release of AVP and activation of V1a, V1b, and V2 vasopressin receptors under physiological and pathological conditions. We make a survey of the role of AVP in: the regulation of the cardiovascular system; body fluid osmolality; natraemia; endocrine regulation; food intake; metabolism; circadian rhythmicity, immunological processes; and in the formation of learning, memory, cognition, and emotional and social behaviours. We also discuss the significance of the inappropriate functioning of the vasopressin system for: the development of cardiovascular diseases; disturbances of the water-electrolyte balance; energy metabolism; inflammatory processes; pain; neurogenic stress; memory disorders; depression; anxiety; autism; and schizophrenia. The structure and biological properties of peptide and non-peptide agonists and antagonists of V1a, V1b and V2 vasopressin receptors are presented and the potential use of copeptin and the current and likely indications for AVP agonists and antagonists in the diagnosis and therapeutics of multiple pathological conditions is discussed.
The neurons secreting oxytocin (OXY) and vasopressin (AVP) are located mainly in the supraoptic, paraventricular, and suprachiasmatic nucleus of the brain. Oxytocinergic and vasopressinergic projections reach several regions of the brain and the spinal cord. Both peptides are released from axons, soma, and dendrites and modulate the excitability of other neuroregulatory pathways. The synthesis and action of OXY and AVP in the peripheral organs (eye, heart, gastrointestinal system) is being investigated. The secretion of OXY and AVP is influenced by changes in body fluid osmolality, blood volume, blood pressure, hypoxia, and stress. Vasopressin interacts with three subtypes of receptors: V1aR, V1bR, and V2R whereas oxytocin activates its own OXTR and V1aR receptors. AVP and OXY receptors are present in several regions of the brain (cortex, hypothalamus, pons, medulla, and cerebellum) and in the peripheral organs (heart, lungs, carotid bodies, kidneys, adrenal glands, pancreas, gastrointestinal tract, ovaries, uterus, thymus). Hypertension, myocardial infarction, and coexisting factors, such as pain and stress, have a significant impact on the secretion of oxytocin and vasopressin and on the expression of their receptors. The inappropriate regulation of oxytocin and vasopressin secretion during ischemia, hypoxia/hypercapnia, inflammation, pain, and stress may play a significant role in the pathogenesis of cardiovascular diseases.
Normal or dysfunctional sexual behavior seems to be an important indicator of health or disease. Many health disorders in male patients affect sexual activity by directly causing erectile dysfunction, affecting sexual motivation, or both. Clinical evidence indicates that many diseases strongly disrupt sexual motivation and sexual performance in patients with depression, addiction, diabetes mellitus and other metabolic disturbances with obesity and diet-related factors, kidney and liver failure, circadian rhythm disorders, sleep disturbances including obstructive sleep apnea syndrome, developmental and hormonal disorders, brain damages, cardiovascular diseases, and peripheral neuropathies. Preclinical studies of these conditions often require appropriate experimental paradigms, including animal models. Male sexual behavior and motivation have been intensively investigated over the last 80 years in animal rat model. Sexual motivation can be examined using such parameters as: anticipatory behavior and 50-kHz ultrasonic vocalizations reflecting the emotional state of rats, initiation of copulation, efficiency of copulation, or techniques of classical (pavlovian) and instrumental conditioning. In this review article, we analyze the behavioral parameters that describe the sexual motivation and sexual performance of male rats in the context of animal experimental models of human health disorders. Based on analysis of the parameters describing the heterogeneous and complex structure of sexual behavior in laboratory rodents, we propose an approach that is useful for delineating distinct mechanisms affecting sexual motivation and sexual performance in selected disease states and the efficacy of therapy in preclinical investigations.
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