Clinical Investigation

Kidney International (1989) 36, 696–701; doi:10.1038/ki.1989.248

Reduced angiotensin receptors and pressor responses in hypotensive hemodialysis patients

Thomas J Moore1, J Michael Lazarus1, Raymond M Hakim1,1, with the technical assistance of Judy Newell1 and Amelia Nunn1

1Endocrine-Hypertension Division and Nephrology Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

Correspondence: Thomas J Moore MD, Endocrinology-Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA.

1Current address is Division of Nephrology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Received 17 November 1988; Revised 27 March 1989; Accepted 8 May 1989.

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Abstract

Reduced angiotensin receptors and pressor responses in hypotensive hemodialysis patients. A sub-set of patients on chronic hemodialysis develop sustained hypotension (systolic pressure < 100 mm Hg). To determine whether this hypotension could be due to altered production of, or sensitivity to angiotensin II (AH), 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 plusminus 2.4 vs. 2.1 plusminus 0.8 ng AI/ml/hr, P < 0.05), AII (56 plusminus 15 vs. 31 plusminus 3 pg/ml), and aldosterone (91 plusminus 35 vs. 21 plusminus 7 ng/dl, P < 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 plusminus 0.4 vs. 3.6 plusminus 1.0% 125I-AII specifically bound; P < 0.03). Binding analysis revealed a single affinity state for the AII receptors which was similar in both groups (Kd = 3.2 plusminus 1.1 for hypotensives vs. 3.8 plusminus 0.7 times 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. Thus, hypotensive dialysis patients display both a reduced pressor response to infused AII and reduced AII receptors on their platelets. This defective AII responsiveness may contribute to the hypotension in these patients.

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