Vasoactive Agents and Blood Pressure Regulation in Sequential Ultrafiltration and Hemodialysis

Abstract

Hypotension is a common and sometimes dangerous side effect of hemodialysis. Its etiology is multifactorial and largely unknown. Earlier studies on the role of endogenous blood pressure regulating agents such as catecholamines and renin have rendered conflicting results. We studied the influence of ultrafiltration and isovolemic hemodialysis separately on the plasma concentrations of the following blood pressure regulating agents: adrenaline, noradrenaline, dopamine, neuropeptide Y, calcitonin gene-related peptide (CGRP), renin (PRA), angiotensin II, vasopressin, aldosterone and Cortisol. During isolated ultrafiltration, plasma levels of two strong vasoconstrictors (noradrenaline and angiotensin II) and one strong vasodilator (calcitonin gene-related peptide, CGRP) increased significantly (noradrenaline 3.24 ± 0.60 nM to 4.31 ± 0.55 nM; p = 0.032, angiotensin II 19.74 ± 3.46 pmol/l to 28.49 ± 7.24 pmol/l; p= 0.047) No symptomatic hypotension occurred. At the end of isovolemic hemodialysis, plasma levels of all the vasoconstricting agents had decreased to pretreatment values, but those of CGRP had continued to rise (from 85.3 ± 17.6 pmol/l to 114.5 ± 25.3 pmol/l, p=0.031). During isovolemic hemodialysis, blood pressure fell to symptomatic levels, but was restored at the end of treatment. The study shows that hemodialysis patients respond to fluid removal by ultrafiltration with an increase in plasma levels of CGRP, noradrenaline and angiotensin II. The net effect is an appropriate vasoconstriction and adequate blood pressure is maintained during isolated ultrafiltration. During hemodialysis, the patients’ blood volumes remained unchanged as evident by a stable hematocrit, the vasoconstrictor hormones returned to normal levels, but in several patients there was a continuous release of vasodilating CGRP. Hypotension, then occurred in these patients due to the imbalance between vasoconstricting and vasodilating factors.