SYMPATHETIC OVERACTIVITY AND CORONARY RISK IN HYPERTENSION

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Interaction between renin and the autonomic nervous system in hypertension

The abnormal distribution of plasma renin values described in established essential hypertension are also found in patients with very early, borderline hypertension. In established hypertension, renin values have been used to draw inferences about the pathophysiology of blood pressure elevation. Within this concept, the low-renin state is considered a volume-dependent (volume expanded) form of hypertension. The high-renin state is viewed as high-resistance hypertension caused by a renin-dependent vasoconstriction. However, the pathophysiology of high- and low-renin borderline hypertension does not follow the prediction from the volume-vasoconstriction theory. The high-renin state is often associated with an increase in cardiac output and normal values of vascular resistance. Even when the cardiac output is normal and the total peripheral resistance is elevated in high renin, the vasoconstriction is not renin-angiotensin dependent. The high-renin borderline and mild hypertension is a state of generalized, increased, sympathetic drive to the heart, blood vessels, and kidneys. After the influence of the autonomic nervous system is removed by pharmacologic blockade, blood pressure in patients with high-renin values becomes normal. To the contrary, pharmacologic antagonization of angiotensin II with a converting enzyme inhibitor does not lead to normal blood pressure values in patients with high-renin. Patients with borderline hypertension with low renin have normal plasma and blood volume values. However, because of decreased compliance of the peripheral capacitance space, the blood volume is shifted from the peripheral to the central (cardiopulmonary) portion of the circulation. Expansion of the cardiopulmonary blood volume causes a larger stretch of cardiopulmonary mechanoreceptors, which, in turn, elicits a preferential inhibition of the sympathetic tone to the kidneys. The low-renin and low sympathetic tone in these patients are the consequence of the expansion of the cardiopulmonary blood volume and not of the total blood volume.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27207/1/0000211.pd

Are different hemodynamic patterns of antihypertensive drugs clinically important?

Since vascular resistance is elevated in hypertension, it is suggested that vasodilators lower the blood pressure by a physiologic mechanism and therefore must be more useful than cardiac output-lowering drugs. This is not entirely correct. Drugs that lower cardiac output are also relative vasodilators, but the vasodilation occurs at a lower level of cardiac output. It is also not necessarily true that all vasodilators are good antihypertensive agents. The clinical profile of a vasodilator depends on its effect on the venous return, cardiac output, regional blood flow, renin-angiotensin system, and sympathetic reflexes. From the viewpoint of hemodynamics, an ideal antihypertensive drug is a vasodilator that does not excessively increase cardiac output, causes no fluid retention, does not induce a great deal of venodilation, and does not elicit substantial neurohumoral counterregulation. Angiotensin-converting-enzyme inhibitors, some calcium antagonists, and some combined alpha/beta-blocking agents come close to satisfying the hemodynamic definition of an ideal antihypertensive drug.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46640/1/228_2005_Article_BF01409481.pd

Abnormalities of autonomic nervous control in human hypertension

The pathophysiology of various stages of hypertension is different. In early hyperkinetic borderline hypertension, the sympathetic drive to the heart and blood vessels is increased while the parasympathetic cardiac inhibition is decreased. The elevated cardiac output, vascular resistance, and blood pressure at that stage can be fully normalized by autonomic blockade. As hypertension advances, a hyperkinetic circulation is less evident, since beta-adrenergic responsiveness and cardiac compliance tend to decrease. Simultaneously hypertrophy of the resistance vessels increases the baseline vascular resistance and the vessels' responsiveness to constrictive stimuli. Eventually a picture of a normal cardiac output/high vascular resistance typical for established essential hypertension emerges. As the blood vessels become hyperreactive, the same degree of vasoconstriction/blood pressure elevation can be achieved with less sympathetic tone. In that phase the sympathetic overactivity is less evident, as the brain resets itself to maintain the same blood pressure elevation with a small amount of sympathetic discharge. While sympathetic overactivity may be less evident in established hypertension, it remains an important pathophysiologic factor, not only for the maintenance of blood pressure, but also for a number of other abnormalities in hypertension. Hypertension is intimately associated with higher levels of pressure-unrelated risk for development of atherosclerosis: dyslipidemia, overweight, and hyperinsulinemia. Furthermore, a number of factors in hypertension favor a poorer outcome from coronary heart disease. These pressure-independent factors increase the risk of coronary thrombosis, arrhythmic deaths, and coronary spasms. Sympathetic overreactivity appears to be crucially implicated in the evolution of this added coronary risk in hypertension. Understanding the pathophysiology of coronary risk and its relationship to sympathetic overreactivity in hypertension is helpful in seeking further improvements in clinical practice. At present antihypertensive treatment is less efficacious in reducing coronary events in hypertension than would be expected. Judicious use of appropriate drugs promises to further improve the efficacy of antihypertensive treatment in those patients who, in addition to high blood pressure, also have other associated risk factors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44622/1/10557_2004_Article_BF00877080.pd

Clinical implications of pathophysiologic changes in the midlife hypertensive patient

Both aging and hypertension decrease cardiac output through a lower stroke volume and a diminished [beta]-adrenergic responsiveness. In parallel, the vascular resistance increases because of vascular hypertrophy. In addition, in hypertension the [alpha]-adrenergic responsiveness is enhanced. Aging and hypertension are also associated with an increase in plasma cholesterol and insulin values. These alterations in cholesterol and insulin levels become particularly pronounced in middle-aged patients with hypertension. [alpha]-Adrenergic-blocking agents have a positive effect on lipids and insulin resistance. The shift toward enhanced [alpha]-adrenergic responsiveness, and the fact that vasodilators do not diminish exercise performance favor the use of [alpha]-blockers as a first drug in middle-aged patients with hypertension. Blood pressure lowering still remains the paramount goal, and these compounds should be used only if proved to be efficacious in a given individual patient.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29650/1/0000739.pd

Introduction

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Transition from high cardiac output to elevated vascular resistance in hypertension

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, [beta]- and [alpha]-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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27206/1/0000210.pd

HOME BLOOD-PRESSURE RECORDING

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Effect of beta adrenoceptor antagonists on baroreceptor reflex sensitivity in hypertension

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Antihypertensive and β‐adrenoceptor antagonist action of timolol

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