Stress‐sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation

Abstract

Edited by: Kate Denton New Findings r What is the central question of this study?Stress-sensitive arterial hypertension is considered to be controlled by changes in central and peripheral sympathetic regulating mechanisms, which eventually result in haemodynamic alterations and blood pressure elevation. Therefore, study of the early stages of development of hypertension is of particular interest, because it helps in understanding the aetiology of the disease. r What is the main finding and its importance?Non-invasive in vivo investigation in ISIAH rats demonstrated that establishment of sustainable stress-sensitive hypertension is accompanied by a decrease in prefrontal cortex activity and mobilization of hypothalamic processes, with considerable correlations between haemodynamic parameters and individual metabolite ratios.The study of early development of arterial hypertension in association with emotional stress is of great importance for better understanding of the aetiology and pathogenesis of the hypertensive disease. Magnetic resonance imaging (MRI) was applied to evaluate the changes in haemodynamics and brain metabolites in 1-and 3-month-old inherited stress-induced arterial hypertension (ISIAH) rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive Wistar Albino Glaxo (WAG) rats (eight male rats). In the 3-month-old ISIAH rats, the age-dependent increase in blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of the abdominal aorta. The renal vascular resistance in the ISIAH rats decreased during ageing, although at both ages it remained higher than the renal vascular resistance in WAG rats. An integral metabolome portrait demonstrated that development of hypertension in the ISIAH rats was associated with an attenuation of the excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats the opposite age-dependent changes were observed. In contrast, in the hypothalamus of 3-month-old ISIAH rats, an increase in energetic activity and prevalence of excitatory over inhibitory neurotransmitters was noticed. The blood flow through the main arteries showed a positive correlation with glutamate and glutamine levels in the hypothalamus and a negative correlation with the hypothalamic GABA level. The blood pressure values were positively correlated with hypothalamic choline levels. Thus, the early development of stress-sensitive hypertension in the ISIAH rats is accompanied by considerable changes both in brain metabolite ratios and in the parameters of blood flow through the main arteries.

Roles of oestradiol receptor alpha and beta against hypertension and brain mitochondrial dysfunction under intermittent hypoxia in female rats

“…Of note, we showed previously that E 2 prevents the elevation of arterial chemoreflex during exposures to CIH in female rats, such that an effect of PPT on peripheral chemoreceptors might be expected. It is also relevant to mention that high blood pressure can compromise the cerebral microcirculation, increasing arterial walls and reducing arterial lumen, and high blood pressure also alters metabolism in the brain cortex . In hypertensive patients, a reduced cortical thickness has been reported, a clear sign of cortical damage probably linked to reduced blood perfusion.…”

“…It is also relevant to mention that high blood pressure can compromise the cerebral microcirculation, increasing arterial walls and reducing arterial lumen, and high blood pressure also alters metabolism in the brain cortex. 40,41 In hypertensive patients, a reduced cortical thickness has been reported, 40 a clear sign of cortical damage probably linked to reduced blood perfusion. In that regard, because our results indicate that only PPT reduces arterial blood pressure, while both PPT and DPN prevent the mitochondrial dysfunction and metabolic switch in the brain cortex, we are confident that the central effect of CIH and ERs agonists is not the result of the induction of (or protection against) high blood pressure.…”

The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats

“…Zfp488 290571 −1.26 zinc finger protein 488 *-genes associated with central nervous system diseases (according to the RGD annotation); ISIAH and WAGrat strains used in the study GABA and glutamate, respectively, are two major inhibitory and excitatory neurotransmitters in the adult mammalian brain [31], which have a direct impact on the sympathetic activity regulation [32]. An earlier study of the metabolic profile in the prefrontal cortex and hypothalamus of 3-month-old ISIAH and WAG rats revealed interstrain differences in the ratio of excitatory and inhibitory brain metabolites, including GABA and glutamate [33]. Based on changes in the expression of the genes Gabra6, Gabrd and Grm2, in common with the metabolomic data, we can assume that there may be changes in the brain stem of ISIAH rats associated with the regulation of sympathetic activity.…”

Neurovisceral regulatory circuits of affective resilience in youth

“…On a very interesting side note, arterial pressure is inversely related to HRV in rodent homologs of adolescence but not pre‐adolescence (Tanaka et al, 2000). A study in rats with stress‐induced arterial hypertension showed that hypertension was associated with an attenuation of the excitatory and energetic activity in the PFC (Seryapina, Shevelev, Moshkin, Markel, & Akulov, 2017). In these hypertensive rats, an increase in energetic activity and prevalence of excitatory (glutamate and glutamine) over inhibitory neurotransmitters was noticed (gamma‐aminobutyric acid (GABA) and glycine).…”