Role of the suprachiasmatic nucleus in the development of hypertension

Despite its alarming prevalence, affecting one out of every three people in the world, the cause of hypertension is mostly unknown (~95% of all cases). Although there is ample evidence suggesting dysfunction of the central biological clock (located in the hypothalamic suprachiasmatic nuclei (SCN) of the brain) in hypertension, almost all related studies conducted at the chronic ‘established’ stage prevent us from concluding whether SCN changes precede or occur as a result of hypertension. This thesis aimed to investigate, by using animal models, whether the observed SCN changes in human patients are a cause or consequence of hypertension. Hereto, spontaneously hypertensive rats (SHRs) served to test whether SCN changes are a cause for their hypertension or not. In contrast, the 2 Kidney 1 Clamp (2K1C) model in Wistar rats was used to induce hypertension and examine whether the SCN changes due to peripheral changes (i.e., kidney dysfunction). Results showed SCN dysfunction in SHRs occurs before and during hypertension, while no similar changes were found in the 2K1C model. A neuroanatomical analysis confirmed that SCN changes correlate with hypertension onset in SHRs.
Consequently, investigation of SCN’s downstream pathways, particularly of brainstem parasympathetic systems in SHRs, indicated an early SCN-NTS axis dysfunction. Hereby, exercise might potentially mitigate the symptoms of hypertension. Finally, the analysis of circadian and fractal activity regulations in pre-hypertensive SHRs also indicated intrinsic SCN changes, suggesting SCN dysfunction as a cause of hypertension. Overall, the thesis supports the idea that SCN changes may cause hypertension rather than the reverse, providing insights for future research and hypertension management in humans.