Functional changes of the SCN in spontaneous hypertension but not after the induction of hypertension

Abstract

The present study investigates the circadian behavior of spontaneously hypertensive rats (SHRs) during the pre-hypertensive and hypertensive stage, with the aim to gain insight into whether observed changes in the functionality of suprachiasmatic nucleus (SCN) in the hypertensive state are cause or consequence of hypertension. Four types of animals were used in this study: (1) SHRs which develop hypertension genetically; (2) their normotensive controls, Wistar Kyoto rats (WKYs); (3) Wistar rats whereby hypertension was surgically induced (2 Kidney 1 Clamp (2K1C) method); and (4) sham-operated control Wistar rats. Period length and activity levels and amplitude changes of locomotor and wheel running activity were determined, in constant conditions, as a measure of the functionality of the SCN. Hereto two conditions were used, constant darkness (0 lux) and constant dim (5 lux) light. SHRs showed a shortened period of their locomotor and running wheel activity rhythms in constant darkness during both pre-hypertensive and hypertensive stages and exhibited period lengthening in constant dim light conditions, only during hypertensive stages. Total amount as well as the amplitude of daily running wheel rhythms showed an inverse correlation with the period length, and this relation was significantly different in SHRs compared to WKYs. None of the aforementioned changes in circadian rhythms were observed after the surgical induction of hypertension. The present findings suggest early functional changes of the SCN in the etiology of spontaneous hypertension.

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

“…Furthermore, the present observations show that after the development of hypertension several of these changes are reversed. These observations are in agreement with our previous observations that the functionality of the SHR SCN had already changed before the animals established hypertension (Yilmaz et al, 2018). Taken together these observations indicate that early changes in the SCN may contribute to the development of hypertension.…”

“…All these observations imply the importance of VIP signaling for activity-related cardiovascular regulation, besides maintaining the synchrony within the SCN. In accordance with the above literature, SHRs have abnormalities in blood pressure and heart rate rhythms (Minami et al, 1988b;Munakata et al, 1990) and they have shorter activity rhythms and an increased amplitude of their locomotor activity rhythm in constant darkness (Yilmaz et al, 2018). Moreover, by taking into account the neuro-anatomical changes described here it is highly tempting to speculate on a crucial role for the interplay between two different VIP subcompartments and the AVP subdivision of the SCN for regulation of circadian rhythms in relation to blood pressure control (Figure 7).…”

“…6). It is tempting to correlate these changes with the changes of running wheel activity, that are increased in SHR in constant dark conditions as compared to normotensive rats, while 2K1C rats' activity level for wheel running was decreased compared to sham-operated controls (Yilmaz et al, 2018). Taken together the results may imply that the VIP levels in the different VIP regions of the SCN are correlated with the level of activity in animals in different hypertension models.…”

“…They have an inverted daily rhythm in blood pressure, but not heart rate after the establishment of hypertension (Minami et al, 1988a;Munakata et al, 1990). The amplitude of their daily locomotor activity as well as their blood pressure rhythm is increased when they get hypertensive (Canal-Corretger et al, 2001;Yilmaz et al, 2018). SHRs have more VIP in their SCN (Peters et al, 1994) and the number of AVP neurons was found decreased in wild-type hosts 8 months after receiving an SCN graft of hypertensive animals (Eilam et al, 1994).…”

Early changes of immunoreactivity to orexin in hypothalamus and to RFamide peptides in brainstem during the development of hypertension

“…Three sets of experiments were conducted. In the first set of experiments, after 2 weeks of acclimatization, 10-weeks old male Wistar albino rats underwent 2K1C surgery to induce hypertension (n=5) or received sham operations (n=4) as described elsewhere (40,41). Blood pressure and heart rate measurements were performed two weeks after the induction of hypertension or sham surgery.…”