Transition from high cardiac output to elevated vascular resistance in hypertension

Abstract

The early phase of hypertension (borderline hypertension) is characterized by a hyperkinetic circulation caused by excessive sympathetic drive and decreased parasympathetic inhibition to the heart. In later phases the cardiac output becomes normal, but the hypertension is still neurogenic, as demonstrated by the fact that continued pharmacologic parasympathetic, β- and α-adrenergic inhibition normalizes the blood pressure. In both of these phases of the process, plasma norepinephrine values are elevated. These patients also show characteristic behavioral patterns; they are outward oriented, submissive, but experience unexpressed anger and frequently harbor hostile feelings. In late phases of hypertension the cardiac output is normal and the total peripheral resistance is elevated. This hemodynamic transition can be explained by a secondary response to elevated blood pressure. The heart becomes less responsive as a result of altered receptor responsiveness and decreased cardiac compliance, whereas the responsiveness of arterioles increases because of vascular hypertrophy, which leads to changes in the wall-to-lumen ratio. However, one observation eludes explanation: the absence of plasma norepinephrine elevation in later phases of hypertension. We propose a new conceptual framework to explain the disappearance of elevated plasma norepinephrine in the course of hypertension. The concept is based on a wide range of observations with the use of various receptor-blocking agents during neurogenic pressor responses. Invariably, the blood pressure response is preserved, but the hemodynamic pattern can be altered from a high cardiac output to high total peripheral resistance or vice versa. The “blood pressure-seeking behavior” of the central nervous system suggests that the negative feedback to the central nervous system is pressure and not flow related. If the central nervous system indeed seeks to obtain a certain pressure and maintains the high blood pressure in early phases by an elevation in cardiac output, later as structural arteriolar changes evolve and the arterioles become hyperresponsive, the same blood pressure elevation could be achieved with less sympathetic drive, and the plasma norepinephrine values return to the normal range.