The role of catechollamines in the pathogenesis of essential hypertension

Abstract

BACKGROUND: Even though essential hypertension has been known for over a century, its pathophysiology and management remains a problem. It has been suggested that adrenaline plays a role in the pathogenesis of essential hypertension. According to the adrenaline hypothesis, excessive stimulation of the adrenomedullary hormonal system can contribute to the development of essential hypertension by augmenting sympatho-neuronal noradrenaline release. However, current literature on the admissability of the adrenaline hypothesis as a cause for hypertension is mixed and at times conflicting. OBJECTIVES: The aim of this study is to demonstrate that the adrenaline hypothesis is a workable theory that underpins hypertension. It comprises of three substudies, the first study involves humans as a model, while the second and the third studies involve spontaneously hypertensive rats (SHR) as models for experimentation. It aims to prove the presence of sympathetic over-activity in young, pre-hypertensive and young, mildly hypertensive Malaysians. It also intends to prove that removal of circulating adrenaline via adrenal demedullation or the administration of an adrenaline synthesis enzyme-inhibitor, Phenylethanolamine-Nmethyltransferase (PNMTI) will result in reduced blood pressure in SHRs. METHODS: The study comprises of three arms, one human and two animal studies. 484 subjects were screened from a primary outpatient medical facility, 97 subjects and age-matched controls were recruited into our human study. Simple demographic data were recorded, blood samples taken for plasma catecholamine and other cardiovascular risk factor variables and blood pressure recordings were observed. 2 groups of spontaneously hypertensive rats were then put through either adrenal demedullation or PNMTI administration along with age- and weight-matched controls. RESULTS: Our study has shown that there is increased plasma adrenaline in young, pre- and mildly hypertensive subjects. Our study have also shown that adrenal demedullation and administration of PNMTI will consistently result in sustained blood pressure reduction as proposed by our hypotheses. We have also shown that the cardiovascular risk factor variables associated with hypertension were significantly increased in our pre- and mildly hypertensive subjects compared to our age- and BPmatched controls. IMPORTANCE: This study shows that adrenaline over-activity is associated with mild hypertension in the young and that removal of the adrenaline drive will result in sustained blood pressure reduction. It has wide-ranging implications especially towards the clinical application of measures to reduce circulating adrenaline levels in order to treat hypertension.