The proposed research is based on our previous studies which defined the effects and interactions of long-term hypertension and aging on the myocardium and suggested that factors in addition to pressure-overload affect hypertrophy in spontaneously hypertensive rats (SHR). Considering the evidence implicating specific factors, we wish to test the hypothesis that interventions involving 1) adrenergic cardiac nerves, 2) cardiac beta receptors, or 3) the peripheral vasculature prevent or modify specific myocardial alterations. Data will be obtained on senescent SHR and normotensive Wistar-Kyoto rats which have been either sympathectomized during early life, or treated with either a cardioselective beta antagonist or a peripheral vasodilator from the time of weaning. Using electron microscopy in conjunction with morphometric, stereological and cytochemical methods, we hope to discover which of the factors associated with hypertrophy relate to the various changes characteristic of long-term hypertension and aging; at the same time we will determine whether they can be prevented or modified with specific types of interventions. As a corollary to these studies, myocardial contractility and metabolism will be assessed in vitro in left ventricular papillary muscles. It is envisioned that the structural alterations attributed to hypertension and aging may affect the intrinsic properties of the myocardium. Accordingly, it will be possible to correlate structure and function, and to establish whether any of the interventions modify myocardial alterations. The relationship of the coronary circulation to structural and functional changes will be explored by 1) measuring regional myocardial blood flow under conditions of maximal vasodilation and stress and 2) evaluating coronary artery morphology.