EFFECTS OF NONPEPTIDE V_1aAND V₂ANTAGONISTS ON BLOOD PRESSURE FAST OSCILLATIONS IN CONSCIOUS RATS

Abstract

This paper describes the effects of vasopressin nonpeptide selective V1a (OPC-21268) and V2 (OPC-31260) antagonists on fast blood pressure (BP) oscillations in conscious non-haemorrhaged and haemorrhaged rats. Equidistant sampling at 20 Hz allowed direct spectral analysis of BP on 30 overlapping 2048 point-time series. In non-haemorrhaged rats, V1a antagonist (5 mg/kg; i.v) reduced BP and low-frequency (LF-BP) component while subsequent administration of V2 antagonist (1 mg/kg; i.v) reversed these changes and enhanced the very low-frequency (VLF-BP) component. In haemorrhaged rats (5-15 ml/kg/min) V2 antagonist pre-treatment enhanced the VLF-BP component during normotensive bleeding, while the V1a antagonist pre-treatment modified BP variability after hypotensive haemorrhage by enhancing the HF-SBP component. The results suggest that under normotensive conditions vasopressin by the stimulation of both V1a and V2 receptors buffers BP variability in the VLF-BP frequency domain. In addition, under hypotensive conditions vasopressin, by the stimulation of V1a receptors buffers the respiration-induced HF-BP oscillation.

Effects of Nonpeptide and Selective V1 and V2 Antagonists on Blood Pressure Short-Term Variability in Spontaneously Hypertensive Rats

“…(29). We also found that under basal conditions the V 2 antagonist does not affect BP variability in a dose of 1 mg / kg, i.v., although it produces water diuresis.…”

“…Furthermore, V 1 receptors have been found in the area postrema, a site of the brain deprived of the blood brain barrier associated with the modulation of the baro-receptor reflex sensitivity (27, 31 -34). We have previously reported that V 1 -and V 2 -receptor antagonists enhance VLF-BP variability in normotensive rats under basal conditions and after the stimulation of vasopressin release by hemorrhage (29), suggesting that both vascular V 1 -receptor and renal V 2 -receptor subtypes are implicated. The present results in SHR with the same doses of vasopressin antagonists show that although in resting conditions V 1 antagonist decreased BP, it modified VLF-BP variability only after massive hemorrhage; and likewise, in normotensive rats, this effect invoved V 1 -and V 2 -receptor subtypes.…”

“…Random screening of chemical compounds resulted in development of orally active and highly selective antagonists at V 1 , V 2 , and V 3 receptor sites with no agonist properties (28). By studying the effects of novel V 1 (OPC-21268) and V 2 (OPC-31260) antagonists on BP short-term variability in normotensive rats, we have provided evidence that vasopressin contributes to fast control of BP and buffers BP short-term variability under basal and hypovolaemic conditions (29).…”

“…Signal processing and the spectrum analysis were described in detail elsewhere (29). Cardiovascular parameters (systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR) were sampled equidistantly at 20 Hz, allowing direct spectrum analysis using fast fourier transform (FFT) over 2048 point time series.…”

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

“…In the present study, we did not apply an osmotic or a hypovolemic challenge to induce intranuclear and systemic release of VP from neurons located in the magnocellular part of the PVN. Moreover, the increase in BP variability observed in rats over-expressing V1aR in this study cannot be attributed to any peripheral effect of VP since peripherally released VP exerts the opposite effect and buffers BP variabilityby enhancing BRS (Japundzic-Zigon, 2001). The present finding, that selective vasopressin V1a receptor antagonist microinjected in PVN of wild type rats and rats over-expressing V1a receptors respectively, prevented or reduced the increase in LF BP variability by stress, suggests that V1a receptors in the PVN participate in the genesis of stress-induced increases in LF-BP variability.…”