Neuropeptide changes in the suprachiasmatic nucleus are associated with the development of hypertension

Abstract

Human postmortem studies as well as experimental animal studies indicate profound changes in the suprachiasmatic nucleus (SCN) in several pathological conditions. In addition, observations in experimental animals show that the SCN peptides, vasopressin (VP) and vasoactive intestinal peptide (VIP) are essential for adequate rhythmicity. These data prompted us to investigate whether changes in these neuronal populations are the cause or consequence of hypertension. Changes in blood pressure and levels of neuropeptide expression in the SCN were determined during the development of hypertension in spontaneous hypertensive rats (SHR), 2K1C reno-vascular induced hypertensive animals and their respective controls. During the pre-hypertensive stage (5 weeks of age), the VIP and AVP content was higher and the somatostatin (SOM) content was lower in the SHR SCN. At the onset of hypertension (12 weeks of age), when blood pressure levels had just reached ~140 mmHg, AVP and SOM content in the SCN was not different anymore in SHRs compared to control, but VIP was still higher. After 16 weeks, the AVP content was decreased, but SOM was increased and the overall level of VIP in the SCN was still higher in SHRs compared to controls. None of the aforementioned changes in the SCN was observed after induction of hypertension in the 2K1C model. However, while VIP was increased in the NTS projecting medial region of the SCN in SHR animals only after the establishment of hypertension, VIP was decreased in the same region in the 2K1C induced hypertensive rats. Consequently, the present findings confirm previous studies in human and rat indicating that changes in the SCN are strongly associated with the development of hypertension. In addition the changes in peptide content in the 2K1C animals indicate that the SCN is also able to respond to increases in blood pressure.

Role of Circadian Rhythm and Impact of Circadian Rhythm Disturbance on the Metabolism and Disease

“…There is a regulatory relationship between neurotransmitters and circadian behavior, such as vasopressin and vasoactive peptides, which are directly related to the circadian rhythm of blood pressure. 48 Almost all SCN neurons express g-amino butyric acid (GABA), an inhibitory neurotransmitter. 49 As the principal circadian system neurotransmitter, GABA affects circadian rhythm control through the specific inhibition of GABA receptors.…”

A wrinkle in time: circadian biology in pulmonary vascular health and disease

“…However, there does appear to be a role for peripheral-tissue= level expression of clock genes in maintenance of systemic vascular health (30), summarized recently (156). Still, there is compelling human data that associates changes in SCN activity -primarily defined as changes in the vasopressin signaling axis effect on peripheral dopamine and epinephrine release -with resulting elevated systemic blood pressure (221). It is unclear if this is cause or effect, however, as systemic hypertension can cause independent changes to SCN activity itself.…”

Vasopressin: An output signal from the suprachiasmatic nucleus to prepare physiology and behaviour for the resting phase

“…The idea of a less active SCN in hypertensive people is supported by the observation that hypertension is associated with lower melatonin levels at night, 110 as well as by the observation that nightly melatonin treatment lowers blood pressure in hypertensive patients 111 . Interestingly, spontaneously hypertensive rats show higher VP immunoreactivity in the SCN during the pre‐hypertensive state, but show a decrease after 16 weeks, when rats have already developed hypertension 112 . In addition, hypertension is a highly prevalent condition during ageing (around 70%).…”

“…Interestingly, spontaneously hypertensive rats show higher VP immunoreactivity in the SCN during the pre-hypertensive state, but show a decrease after 16 weeks, when rats have already developed hypertension 112. In addition, hypertension is a highly prevalent condition during ageing (around 70%).…”