On the role of insufficient mitochondrial energy production in primary hypertension: the neurogenic constitutive of the pathogenesis

摘要

There are accumulated evidences on existence of an imbalance between energy production and consumption in tissues in primary hypertension resulting in insufficient compensation of energy and its deficiency in cells (human essential hypertension, spontaneous hypertension in rats, SHR). An origin of these abnormalities resides in an alteration of cell mitochondrion ATP-synthetic function which ground is calcium overload of mitochondria due to increased cytosolic calcium redundantly entering into mitochondria and development of insufficiency of mPT pore removing calcium from matrix of the organells. There is an energy production deficiency in brain tissue of individuals with primary hypertension that is not initially caused by alteration of cerebral blood circulation of ischemic type. The mentioned energy abnormality is determined by decreased ability of brain mitochondria to synthesize ATP as a result of their calcium overload due to altered cell calcium handling in hypertension (so called membrane defect). In these conditions the registered normal or insignificantly changed cerebral blood flow in primary hypertension may be a result of systemic blood pressure increase in response to energy deficiency in brain tissue. Mechanisms mediating development of systemic hypertension include as the most important activation of vasomtor centers of brain stem. Other systems influencing vascular flow and peripheral resistance also contribute. Among those redundant (under conditions of calcium overload) production of oxidative radicals by mitochondria canceling vasorelaxing effect of NO should be specifically mentioned. The structural remodeling of peripheral circulation including rarefaction of capillary network provides for irreversibility of hypertension.