Franz Volhard lecture. Increased systemic vascular resistance and primary hypertension: the expanding complexity

Polygenetic predisposition is a key factor in the multifactorial disorders of primary hypertension. It is suggested that endothelial cell abnormalities are the major factors responsible for the increase in total systemic vascular resistance that leads to an elevation in arterial blood pressure. Thus, resetting of the arterial baroreceptors could be a consequence of endothelial-mediated changes in mechano-electrical transduction in the arterial mechanoreceptors. In consequence, inhibition of the vasomotor centers would be diminished and the resulting neurohumoral excitation would constrict the systemic resistance blood vessels. Later, as left ventricular hypertrophy develops, the inhibitory input of the cardiac mechanoreceptors is also reduced. In normal endothelial cells there is a predominant formation and release of vascular smooth muscle relaxing and growth-inhibiting factors. However, it is proposed that genetic changes lead to a predominate formation of endothelium-derived contracting factors and mitogens. The former would augment the neurohumoral vasoconstriction. The latter, aided by the increased arterial pressure and the augmented output of norepinephrine, would lead to structural alterations in the arterial vessels, thus reducing the lumen area, amplifying the vasoconstrictor response to contractile agents and limiting vasodilation. In this way the hypertension would be perpetuated.