Intracerebroventricular administration of the angiotensin II receptor antagonist saralasin reduces respiratory rate and tidal volume variability in freely moving Wistar rats

Abstract

The possible importance of intra-individual variations in respiratory rate and tidal volume has recently gained interest in psychiatric research, as a result of the observations that patients with panic disorder or premenstrual dysphoric disorder display enhanced respiratory variability as compared to controls. Although the role of brain neurotransmitters in the regulation of breathing has been extensively studied, as yet data on the central regulation of respiratory variability is sparse. Prompted by previous studies indicating that angiotensin II (ANG II) may influence ventilation as well as anxiety, we have studied the effect of intracerebroventricular administration of an ANG II receptor antagonist, saralasin, on respiratory variability in unrestrained, freely moving male Wistar rats. Treatment with saralasin, 5 μg dissolved in 1 μl saline followed by 9 μl saline in each lateral cerebral ventricle, did not influence tidal volume, but markedly reduced tidal volume variability ( p=0.0005), as compared to saline injections (10 μl). Respiratory rate was reduced by saralasin ( p=0.02), and there was also a non-significant tendency for a reduction in respiratory rate variability. Both minute volume ( p=0.005) and volume/10 s variability ( p=0.0006) were reduced. It is suggested that ANG II in the brain of Wistar rats may regulate respiratory rate and tidal volume variability.