Decreased Beta-adrenoreceptor responsiveness as related to age, blood pressure, and plasma catecholamines in patients with essential hypertension.

Abstract

SUMMARYThe role of the sympathetic nervous system as it relates to adreooreceptor-mediated hemodynamic responses was investigated in patients with essential hypertension and in normal subjects of similar age. An age-related increase in plasma norepinephrine (PNE) concentrations observed in 36 recumbent normal subjects (r = 0.623, p < 0.001) was not found in 56 patients; the latter included some young patients with high values. Sympathetic overactivity in patients (n = 24) as compared with normotensive subjects (n = 20) was suggested by a greater increase in PNE upon standing (242 ± 34 vs 155 ± 25 pg/ml (SEM), p < 0.05) and persistently higher plasma eplnephrine (PE) concentrations at rest and during equieffecrire exercise (p < 0.05). In patients, PNE was directly related to systolic (r = 0.57, p < 0.01) and diastolic (r = 0.53, p < 0.01) blood pressure. Older age was associated with diminished exercise tachycardia and increased blood pressure responses to exercise, which were both more pronounced in hypertensive patients. This higher pressure/lower heart rate pattern was paralleled by an age-related decrease in isoproterenol sensitivity in normal subjects ( system as well as vascular tone are, in part, controlled via |8 and a adrenoreceptors. The response of the target organ is therefore the result of a balance between neural activity and receptor responsiveness. Sympathetic nervous activity and changes therein are reflected in plasma catecholamine concentrations 1 and in heart rate, particularly when parasympathetic tone is minimized during strenuous physical exercise. Beta-adrenoreceptor response can be assessed selectively by heart rate stimulation with isoproterenol.* To obtain a more integrated view of the sympathetic nervous system involvement and its interaction with adrenoreceptor-mediated cardiovascular functions, heart rate and blood pressure were measured and compared with plasma catecholamine concentrations in age-matched groups of normotensive and hypertensive subjects at rest and during exer-

β-adrenergic receptor density and function in left ventricular hypertrophy in young essential hypertensives

“…7 Even though some initial reports indicated an increased ␤ 2 -adrenergic chronotropic response in patients with essential hypertension, 25,26 a number of recent studies have shown that cardiac ␤ 2 -adrenergic response is in fact decreased in hypertensive patients. 8,27 The aetiology of this decreased responsiveness is probably multifactorial, but alterations in the ␤-adrenergic receptor-adenilylcyclase system appear to be a contributing factor. Studies performed in animal models of genetic and acquired hypertension have shown a desensitization of cardiac adrenergic receptors 28,29 and that cardiac sympathetic neuronal function deteriorates in association with cardiac ␤-adrenoceptor down-regulation.…”

Effects of Nifedipine and Enalapril on Cardiac Autonomic Nervous Function during the Tilt Test in Elderly Patients with Hypertension.

“…These findings indicate that nifedipine influences cardiac autonomic nervous function during tilting. Elderly people have reduced baroreflex sensitivity and elevated PNE with decreased ~3-adrenoreceptor responsiveness at baseline (13,14). Chronic nifedipine administration promotes the reduced R-adrenoreceptor responsiveness and elevation of PNE with increased cardiac sympathetic activity (15)(16)(17).…”

Cardiac autonomic modulation and incidence of late potentials in essential hypertension: role of age, sex, ventricular mass and remodeling

“…8,9 Whether the activity of the autonomic nervous system to the heart is influenced by aging in hypertensive patients remains uncertain, owing to discrepancies in the results of different methods currently used to evaluate the sympathetic control of the cardiovascular system in these patients. In fact, in spite of an increased noradrenaline spillover, 10,11 total heart rate variability (HRV) and the variability of low-frequency oscillations were markedly reduced in elderly healthy subjects, 12,13 suggesting that endorgan responsiveness may be impaired with age, 14 because of alterations of the ␤-adrenergic receptor and/or its postreceptor signal transduction pathway.…”