Vasopressin and v1br gene expression is increased in the hypothalamic pvn of borderline hypertensive rats

Abstract

Vasopressin (VP) is a neurohypophyseal peptide best known for its role in maintaining osmotic and cardiovascular homeostasis. The main sources of VP are the supraoptic and paraventricular (PVN) nuclei of the hypothalamus, which co-express the vasopressin V1a and V1b receptors (V1aR and V1bR). Here we investigate the level of expression of VP and VP receptors in the PVN of borderline hypertensive rats (BHRs), a key integrative nucleus in neuroendocrine cardiovascular control. Experiments were performed in male BHRs and Wistar rats (WR) equipped with radiotelemetry device for continuous hemodynamic recordings, under baseline conditions and after saline load without or with stress. The autonomic control of the circulation was evaluated by spectral analysis of blood pressure (BP) and heart rate (HR) variability and baro-receptor reflex sensitivity (BRS) using the sequence method. Plasma VP was determined by radioimmunoassay, and VP, V1aR and V1bR gene expression by RT-qPCR. Under baseline conditions, BHRs had higher BP, lower HR and enhanced BRS in respect to WRs. BP and HR variability was unchanged. In the PVN, overexpression of VP and V1bRs genes were found and plasma VP was increased. Saline load downregulated V1bR mRNA without affecting VP mRNA expression, plasma VP and the BP. Adding stress increased BP, BP and HR low frequency sympathetic spectral markers, decreased plasma VP without altering the level of expression of VP and VP receptors in PVN. It follows that overexpression of VP and V1bR in the PVN is a characteristic trait of BHR, and that sympathetic hyperactivity underlies stressinduced hypertension.

The Paraventricular Nucleus of the Hypothalamus in Control of Blood Pressure and Blood Pressure Variability

“…In these rats no changes in VP and VR gene transcription in the PVN was noted. Moreover, systemic VP release was decreased, refuting involvement of VP in stress-induced hypertension ( Savić et al, 2020 ).…”

“…We have investigated the neurochemical contribution of the PVN to short-term BPV, and found that both VP and OT modulate short-term BPV. Using pharmacological and genetic tools in conscious rats we have shown that VP modulates BPV in a complex manner: peripherally as a hormone and centrally as neurotransmitter/modulator ( Japundzic-Zigon, 2001 , 2013 ; Japundzić-Zigon et al, 2004 , 2018 , 2020 ; Milutinović et al, 2006a , b ; Stojicić et al, 2008 ; Milutinović-Smiljanić et al, 2013 ; Lozić et al, 2016 ; Savić et al, 2020 ). Using spectral analysis of BPV, we found that peripheral administration of non-peptide and selective V1aR or V2R antagonists to conscious normotensive rats under baseline physiological conditions increases BPV, suggesting a buffering role for VP in the VLF domain ( Japundzic-Zigon, 2001 ).…”

“…Borderline hypertensive rats (BHR) have a genetic predisposition for hypertension and will develop it when exposed to environmental challenges. Under baseline physiological conditions BHRs have increased expression of VP and V1bR in the PVN and consequently increased plasma VP concentrations, as a constitutive trait ( Savić et al, 2020 ). Spectral markers of sympathetic activity toward blood vessels, LF-BP, and the heart, LF/HF-HR, are comparable to normotensive rats under baseline physiological conditions, suggesting that increased expression of V1bR and VP in BHRs is confined to magnocellular (endocrine) portion of the PVN affecting plasma VP only.…”

Effects of salt and stress on blood pressure parameters and antioxidant enzyme function in the heart and aorta of borderline hypertensive rats

“…It seems that in BHRs, an elevated level of circulating plasma noradrenaline changes vascular reactivity and contributes to differential haemodynamic adaptations (Fuchs et al., 1998 ). The BHRs are characterized by a high plasma concentration of vasopressin (Savic et al., 2020 ), and exogenous vasopressin provoked pressor‐induced cardiac hypertrophy (Fuchs et al., 1998 ). Furthermore, crowding stress elevates plasma corticosterone and accelerates development of hypertension in juvenile male (Bernatova et al., 2018 ) and female BHRs (Slezak et al., 2014 ).…”

“…Signals from the radiotelemetry devices were transmitted to a data acquisition and analysis system composed of a Data Exchange arterial blood pressures and the pulse interval (PI) or its inverse value, heart rate (HR), were derived from the arterial PP wave as the maximum, minimum and interbeat interval, respectively. The signal length used for analysis was 409.6 s (Savic et al, 2020).…”