LOOK ON THE PATHOGENESIS OF HYPERTENSION - RESETTING ON CELLULAR, ORGAN AND SYSTEMIC LEVELS

Developing the ''membrane concept'' of primary (essential) hypertensio n the author proceeds from the following: The pathogenetic basis of th is form of hypertension is widespead (i.e. not limited to one type of cells) membrane iontransport abnormalities that jointly reflect the sh ifting in the values of several intracellular constants (Ca-i(2+), pH( i)), maintained by the cell membranes. Membrane alteration mentioned a bove has a genomic source and is initiated by a factor whose impact is mediated by protooncogenes. The specific functions of the cells are p reserved in spite of constantly increased cytoplasmic free calcium by means of a kind of cell adaptation, i.e. cell resetting. The latter cr eates by adaptive changes in the mechanisms of cell calcium homeostasi s as well as by changes in hormone - target interactions. Under condit ions of a widespead expression of membrane alterations the influences from altered cell targets are the main source of sympathetic system ac tivation, the increasing rate of corticosteroid secretion, hyperinsuli nemia and other neurohormonal changes inherent to this pathology. Chro nic increase of the systemic blood pressure is provided by the subsequ ent development of the kidney resetting, i.e. shifting of the renal ex cretory function curve with respect to higher systemic blood pressure (A.Guyton). Resetting of the kidney makes normal salt and water output possible and at the same time maintains (by a feed-back mechanism) th e corresponding (heightened) blood pressure. The rise of the systemic blood pressure brings about resetting of various negative feed-back sy stems including arterial baroreceptors (J.Mc Cubbin et al., B.Cribben et al.), the renal renin-release threshold (Y.Kaneko et al.) etc. Furt her stabilization (as well as irreversibility) of hypertension achieve d by its structural reinforcement (B.Folkow) (arterial wall hypertroph y and kidney sclerosis). An important stabilizing factor of hypertensi on is the necessity of hightened perfusion pressure for preserving cer ebral blood glow autogregulation under conditions of high cerebrovascu lar resistance (C.Dickinson).