Reduced angiotensin receptors and pressor responses in hypotensive hemodialysis patients

Abstract

A sub-set of patients on chronic hemodialysis develop sustained hypotension (systolic pressure less than 100 mm Hg). To determine whether this hypotension could be due to altered production of, or sensitivity to angiotensin II (AII), we measured plasma renin (PRA), AII, and aldosterone in nine hypotensive and nine normotensive dialysis patients; we also assessed their sensitivity to infused AII and studied AII binding to their platelets as an indicator of AII receptors on vascular smooth muscle. All studies were performed just before dialysis when subjects were relatively volume-expanded. Hypotensives had higher PRA (5.7 +/- 2.4 vs. 2.1 +/- 0.8 ng AI/ml/hr, P less than 0.05). AII (56 +/- 15 vs. 31 +/- 3 pg/ml), and aldosterone (91 +/- 35 vs. 21 +/- 7 ng/dl, P less than 0.05) than did normotensives. During AII infusion at 1, 3, 10, and 30 ng/kg/min for 15 minutes each, hypotensives displayed a significantly blunted pressor effect across the range of AII doses. In parallel with this, hypotensives showed reduced AII receptors on their platelets compared to normotensives (0.8 +/- 0.4 vs. 3.6 +/- 1.0% 125I-AII specifically bound; P less than 0.03). Binding analysis revealed a single affinity state for the AII receptors which was similar in both groups (Kd = 3.2 +/- 1.1 for hypotensives vs. 3.8 +/- 0.7 x 10(-10) M for normotensives). The two groups had similar levels of plasma catecholamines, similar slowing of heart rate during AII infusion and no postural hypotension, indicating intact sympathetic nervous system pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuated Cardiovascular Response to Sympathetic System Activation during Exercise in Patients with Dialysis-Induced Hypotension

“…Hypotensive HD patients display even higher plasma catecholamine levels than uremic patients [7,9,26], while the pressor response to noradrenaline infusion is markedly blunted when compared to normotensive HD patients [7,9,26], suggesting the presence of postsynaptic vascular resistance to the sympathetic stimuli and a compensatory sympathetic activation. Previous authors have ascribed this peripheral resistance to catecholamines to a reduced vascular adrenoceptor number and/or function [9].…”

“…There are significant publications on peripheral vascular resistance in patients with ESRD in the literature: the autonomic neuropathy often present in uremia [8], an impaired vascular adrenoceptor function [9], or a decreased vascular response to angiotensin II infusion secondary to a reduced angiotensin II receptor number [26], and others. Hypotensive HD patients display even higher plasma catecholamine levels than uremic patients [7,9,26], while the pressor response to noradrenaline infusion is markedly blunted when compared to normotensive HD patients [7,9,26], suggesting the presence of postsynaptic vascular resistance to the sympathetic stimuli and a compensatory sympathetic activation.…”

Role of nitric oxide in haemodialysis hypotension

“…1987 ) and the precise mechanism underlying this form of hypotension is not known, although autonomic dysfunction and reduced responses to vasoactive substances such as angiotensin II, arginine vasopressin or noradrenaline have been reported as possible causes ( Daul et al . 1987 , Moore et al . 1989 , Carretta et al .…”

Down‐Regulation of Angiotensin II Receptor Subtypes and Desensitization of Cyclic GMP Production in Neuroblastoma N1E‐115 Cells

“…This phenomenon, which is referred to as down-regulation, is usually associated with a concomitant decrease in the functional efficacy of receptor occupancy. Down-regulation of receptors for angiotensin I1 (AngII) has been demonstrated in many of the peripheral target organs for this peptide (Aguilera and Catt, 1981; Moore et al, 1984Moore et al, , 1989 Kitamura et al, 1986). However, in other tissues such as adrenal cortex and liver, AngII has been reported to actually increase the density of its own receptors (Sernia et al, 1985).…”