Reduced Angiotensin Receptors and Pressor Responses in Hypotensive Hemodialysis Patients

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)