Early versus late onset of therapy. Experiences from animal studies

Established primary hypertension is characterized by an "upward structural resetting," that encompasses all pressure-exposed cardiovascular sections. This also affects several of the dominating barostat mechanisms, such as those based on the cardiovascular baroreceptors and volume receptors and on the renal excretory function. One major long-term goal in antihypertensive treatment, therefore, is to achieve reversal and, if possible, normalization of this structural resetting, the more so because such reversal would also interrupt the positive feedback interaction with functional excitatory mechanisms. It is, however, very difficult to analyze precisely the rate and extent of structural cardiovascular reversal in humans, and also whether some antihypertensive drugs are in these respects more efficient than others. In this respect, model therapy studies in rat primary hypertension offer several advantages, thanks to the greatly compressed time scale, uniform material, and easily controlled conditions. This facilitates the elucidation of such important problems as the relative merits of early versus late treatment and optimal duration and intensity of treatment, as well as which drug actions are most efficient in normalizing cardiovascular design. The relatively few rat model studies of structural cardiovascular reversal so far performed are outlined briefly. It is concluded that extended studies along these lines would be of great value in clarifying some general principles of antihypertensive treatment that are also likely to be relevant to primary hypertension in humans.