A new look at the old mosaic1
The author pays tribute to Dr. Irvine H. Page, whose life was a “mosaic” of key scientific contributions in the field of hypertension and of professional and societal involvement. Important and recent contributions are brought together to confirm the hypothesis, as expressed by Dr. Page in 1937, that the secretions of some endocrine glands, in particular, the adrenal cortex, keep the vascular system in a hyper-reactive state. Evidence is presented to demonstrate that increased peripheral resistance and chronic hypertension are neither due to an increase in cardiac output or plasma or extracellular fluid volume nor arteriosclerotic lesions, but are primarily related to increased arterial sensitivity and responsiveness to pressor agents, such as norepinephrine and angiotensin II. The sodium balance, which is mainly determined by the production of aldosterone in the adrenal cortex, is fundamentally involved in the increased peripheral resistance of hypertension. Since hypertension is the result of disequilibrium between the sympathetic nervous system activity and the state of sensitivity and reactivity of the contractile proteins in the arterial walls, models are proposed based on increased sympathetic nervous system activity, increased activity of the renin-angiotensin system, and a disturbance in aldosterone regulation and sodium transport across cell membranes and which are associated with the increased sensitivity and reactivity of the arterioles.