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.

Automated summary

Hypertension affects over 1 billion individuals worldwide, and the cause is largely unknown. Increased sympathetic nervous system activity is common in hypertensive patients, but the root cause is still unclear. Recent research has found that the neural network controlling sympathetic drive becomes more reactive after exposure to mild challenges, leading to a sensitized hypertensive response. Plasticity in the neural network and the involvement of various factors are necessary for the induction and maintenance of this state. This review discusses the induction and expression of this sensitized hypertensive response in adult animals and the offspring of mothers with prenatal obesity/overnutrition or maternal gestational hypertension, as well as interventions to reverse the effects of stressor-induced sensitization.