Sensitization of Hypertension: The Impact of Earlier Life Challenges: Excellence Award for Hypertension Research 2021.

Hypertension affects over 1 billion individuals worldwide. Because the cause of hypertension is known only in a small fraction of patients, most individuals with high blood pressure are diagnosed as having essential hypertension. Elevated sympathetic nervous system activity has been identified in a large portion of hypertensive patients. However, the root cause for this sympathetic overdrive is unknown. A more complete understanding of the breadth of the functional capabilities of the sympathetic nervous system may lead to new insights into the cause of essential hypertension. By employing a unique experimental paradigm, we have recently discovered that the neural network controlling sympathetic drive is more reactive after rats are exposed to mild challenges (stressors) and that the hypertensive response can be sensitized (ie, hypertensive response sensitization [HTRS]). We have also found that the induction of HTRS involves plasticity in the neural network controlling sympathetic drive. The induction and maintenance of the latent HTRS state also require the functional integrity of the brain renin-angiotensin-aldosterone system and the presence of several central inflammatory factors. In this review, we will discuss the induction and expression of HTRS in adult animals and in the progeny of mothers with prenatal obesity/overnutrition or with maternal gestational hypertension. Also, interventions that reverse the effects of stressor-induced HTRS will be reviewed. Understanding the mechanisms underlying HTRS and identifying the beneficial effects of maternal or offspring early-life interventions that prevent or reverse the sensitized state can provide insights into therapeutic strategies for interrupting the vicious cycle of transgenerational hypertension.