Autonomic nervous system and adrenergic receptors in chronic hypotensive haemodialysis patients.

BACKGROUND: The pathophysiology of chronic hypotension (CH) in uraemia is not elucidated. The possible role of autonomic nervous system dysfunction and adrenoceptor alterations in the pathophysiology of CH in uraemia was evaluated in this study. METHODS: Seventeen hypotensive haemodialysis (HD) patients, 17 normotensive HD patients, and 17 control subjects were studied. We evaluated the integrity of the baroreflex arc (Valsalva manoeuvre), the parasympathetic efferent pathway ('deep-breathing test') and the sympathetic efferent pathway ('hand-grip test'). We also evaluated platelet alpha 2-adrenoceptor and lymphocyte beta 2-adrenoceptor densities (radioligand binding assay), and beta 2-adrenoceptor response (intracellular cAMP generation after isoproterenol stimulation in lymphocytes). RESULTS: Responses to the Valsalva manoeuvre and the deep-breathing test were altered in all HD patients (P < 0.05). Valvalva ratio was lower in hypotensive patients than in normotensive patients (P < 0.01), whereas the pressor response to the hand-grip test was reduced only in hypotensive HD patients (P < 0.01). In haemodialysed patients, basal mean blood pressure (MBP) correlated with MBP increases during the hand-grip exercise (r = 0.59, P < 0.01). Plasma catecholamine levels were elevated in both groups of patients (P < 0.025). Plasma adrenaline levels were higher in hypotensive HD patients than in normotensive patients (P < 0.05). alpha 2- and beta 2-adrenoceptor densities and beta 2-adrenoceptor response were reduced in hypotensive patients (P < 0.05 vs normotensive patients). MBP correlated with alpha 2-adrenoceptor (r = 0.46, P < 0.01) and beta 2-adrenoceptor (r = 0.43, P < 0.025) densities in HD patients. CONCLUSIONS: Normotensive haemodialysed patients have increased plasma catecholamine levels with preserved alpha 2- and beta 2-adrenoceptor numbers, as well as beta 2-adrenoceptor responses. In hypotensive patients, plasma adrenaline levels were even higher; the increased plasma catecholamine levels induced an alpha 2- and beta 2-adrenoceptor downregulation. This downregulation may play a role in the reduced cardiovascular responses to adrenergic stimuli reported in hypotensive HD patients.

Vasoactive hormones in uraemic patients with chronic hypotension.

BACKGROUND: We evaluated the possible role of an imbalance between vasoconstrictor and vasodilator hormones in the pathophysiology of chronic hypotension in uraemia. METHODS: Fourteen hypotensive haemodialysed patients, 14 normotensive haemodialysed patients, and 17 control subjects were included in this study. Plasma renin activity (PRA) and plasma levels of catecholamines, angiotensin II (AII), atrial natriuretic peptide (ANP), and arginine vasopressin (AVP) were measured. RESULTS: The mean time on haemodialysis (HD) was longer in hypotensive patients than in normotensive patients (P < 0.01). Catecholamine levels were higher in the whole group of HD patients than in controls (P < 0.01). Catecholamine levels were higher in hypotensive patients than in normotensive patients, but the differences reached significance only for adrenaline (P < 0.05). PRA and plasma AII levels were higher in hypotensive patients than in the other two groups (P < 0.05), while no differences were observed between normotensive patients and controls. Plasma ANP and AVP levels were higher in HD patients than in controls (P < 0.01), but there were no differences between hypotensive and normotensive patients. In HD patients, mean blood pressure inversely correlated with PRA (r = -0.59, P < 0.01) and plasma AII levels (r = -0.80, P < 0.01). CONCLUSIONS: Our results indicate that in HD patients with chronic hypotension there is an activation of the sympathetic and the renin-angiotensin systems. This activation is probably secondary in an attempt to compensate the vascular resistance to pressor stimuli reported in these patients.