The role of central vasopressin receptors in the modulation of autonomic cardiovascular controls: a spectral analysis study

Abstract

Although it has been suggested that vasopressin (VP) acts within the central nervous system to modulate autonomic cardiovascular controls, the mechanisms involved are not understood. Using nonpeptide, selective V 1a, V1b, and V2 antagonists, in conscious rats, we assessed the roles of central VP receptors, under basal conditions, after the central application of exogenous VP, and after immobilization, on cardiovascular short-term variability. Equidistant sampling of blood pressure (BP) and heart rate (HR) at 20 Hz allowed direct spectral analysis in very-low frequency (VLF-BP), low-frequency (LF-BP), and highfrequency (HF-BP) blood pressure domains. The effect of VP antagonists and of exogenous VP on body temperature (Tb) was also investigated. Under basal conditions, V 1a antagonist increased HF-BP and Tb, and this was prevented by metamizol. V1b antagonist enhanced HF-BP without affecting Tb, and V2 antagonist increased VLF-BP variability which could be prevented by quinapril. Immobilization increased BP, LF-BP, HF-BP, and HF-HR variability. V1a antagonist prevented BP and HR variability changes induced by immobilization and potentiated tachycardia. V1b antagonist prevented BP but not HR variability changes, whereas V2 antagonist had no effect. Exogenous VP increased systolic arterial pressure (SAP) and HF-SAP variability, and this was prevented by V1a and V1b but not V2 antagonist pretreatment. Our results suggest that, under basal conditions, VP, by stimulation of V1a, V1b, and cognate V2 receptors, buffers BP variability, mostly due to thermoregulation. Immobilization and exogenous VP, by stimulation of V1a or V1b, but not V2 receptors, increases BP variability, revealing cardiorespiratory adjustment to stress and respiratory stimulation, respectively. temperature; heart rate; V1a; V1b; V2 antagonist VASOPRESSIN (VP) IS A NEUROHYPOPHYSEAL peptide that acts both as neurohormone and central neurotransmitter/modulator. Peripherally, VP exerts a variety of biological effects in mammals: body fluid balance, blood pressure (BP) control, platelet aggregation, ACTH, aldosterone and clothing factor VIII secretion, liver glycogenolysis, and uterine motility. Centrally, VP affects learning, memory, behavior, and autonomic functions such as BP, body temperature (T b ), and respiration. The role of VP is particularly important in stress (14,25,27), and VP dysfunction was found to contribute to the pathogenesis of cardiovascular disease (28, 35) and to underlie central diabetes insipidus.So far, three types of G protein-linked membrane-bound VP receptor subtypes, V 1a , V 1b , and V 2 , have been cloned and characterized by their primary structure, gene localization, mRNA distribution, physiological function, and pharmacology (4,12,41,47). V 2 receptors have been found only in the periphery; they are positively coupled to adenylcyclase and play a dominant role in the antidiuretic response to VP. V 1a and V 1b receptors have been found both peripherally and in the central nervous system (CNS), where they mediate phospholi...

Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control

“…Similar effects on respiration were obtained with microinjections of the excitatory transmitter L-glutamate into the PVN (Yeh et al, 1997). Also intracerebroventricular injection of VP has been shown to increase HF-BP variability (Milutinović et al, 2006). In our study, the effect of V1aR overexpression in PVN on HF-BP magnitude could reflect an increase in the alveolar surface for blood oxygenation to support the active coping strategy observed in present experiments.…”

“…We have previously reported that central V1a receptors are important in the modulation of the cardiovascular response to stress (Milutinović et al, 2006;Stojičićet al, 2008;Milutinović-Smiljanić et al, 2013). Here we investigate the role of PVN V1a receptors in autonomic adjustment of the cardiovascular system to emotional stress.…”

Proximal colon distension induces Fos expression in oxytocin-, vasopressin-, CRF- and catecholamines-containing neurons in rat brain

“…Whether or not the activation of AVP-containing neurons during noxious colon distension reflects only the anxiogenic component of pain or is more directly related to the integration and processing of pain signals warrants further studies. For instance, there is evidence of cardiovascular effects of vasopressin acting in the brain as a transmitter, in addition to its well-known peripheral vasopressor actions (Milutinović et al 2006). …”

Vasopressin and Oxytocin in Control of the Cardiovascular System

“…pharmacological doses, increases BP [58, 59] while OT was reported to do the opposite [60]. However, application of selective antagonists, peripherally and centrally, revealed that physiological concentrations of VP and OT do not modulate BP under basal physiological conditions and do not participate in the maintenance of BP under basal physiological conditions [58, 59].…”

“…pharmacological doses, increases BP [58, 59] while OT was reported to do the opposite [60]. However, application of selective antagonists, peripherally and centrally, revealed that physiological concentrations of VP and OT do not modulate BP under basal physiological conditions and do not participate in the maintenance of BP under basal physiological conditions [58, 59]. However, V1aR receptor knock-out mice were reported to exhibit lower basal BP values than wild-type controls [61] while OT knock-out mice have been reported to exhibit greater basal BP and heart rate values than wild-type controls [62].…”