HYPOTHALAMIC AND MEDULLARY FUNCTIONAL GENOMICS IN STRESS-INDUCED HYPERTENSION

Neurogenic essential hypertension and its complications are the world’s leading causes of morbidity and mortality. Inheritance and chronic stress have both been found to contribute to the development of hypertension. We propose to investigate the pattern of gene expression in key brain nuclei involved in blood pressure (BP) control in borderline hypertensive rats (BHR) with stress-induced hypertension. BHRs have a family history of hypertension, but will develop it only when they are exposed to chronic environmental stress. Patterns of gene expression in the rostoventrolateral medulla, the nucleus tractus solitarius and the hypothalamic paraventricular nucleus of BHR will be determined by microarray. After selection of genes of interest, we will investigate their role in BP regulation in conscious rats. Under ketamine/xylazine anesthesia viral gene transfer will be used to deliver and modify expression of selected gene in the brain areas of BHR. Effects on cardiovascular parameters will be analyzed under basal conditions and after exposure to stress. Evaluation of the baroreflex and cardiovascular variability will be done using the method of sequences and spectral analysis. In addition, a prospective clinical study on antihypertensive drug efficacy in hypertensive patients along with patient genotypization is proposed to gain insight in the state of the art. The results might indicate new drug targets and contribute to individual optimization of treatment.