The pathologic
hypertrophy of hypertensive
heart disease is related to the quality, not the quantity, of myocardium; the presence of
fibrosis is inevitably linked to structural and functional insufficiencies with increased cardiovascular risk. Elevations in plasma
aldosterone that are inappropriate relative to
dietary sodium, or relative
aldosteronism, are accompanied by suppressed plasma
renin activity, elevation in arterial pressure, and dyshomeostasis of
divalent cations. The accompanying
hypocalcemia, hypomagnesemia, and hypozincemia of
aldosteronism contribute to the appearance of
secondary hyperparathyroidism.
Parathyroid hormone-mediated intracellular
calcium overloading of cardiac myocytes and mitochondria leads to the induction of oxidative stress and molecular pathways associated with cardiomyocyte
necrosis and
scarring of myocardium, whereas the dyshomeostasis of
zinc compromises
antioxidant defenses. This dys-homeostasis of
calcium and
zinc, intrinsically coupling prooxidant
calcium and
antioxidant zinc, raises the prospect for therapeutic strategies designed to mitigate intracellular
calcium overloading while enhancing
zinc-mediated
antioxidant defenses, thus preventing adverse myocardial remodeling with
fibrosis, associated diastolic dysfunction, and
cardiac arrhythmias.