Dominique Schohn

Mitogenic activity on human arterial smooth muscle cells is increased in the plasma of patients undergoing hemodialysis with cuprophane membranes.

During hemodialysis on cuprophane membranes, platelets are activated and release in plasma alpha-granule-specific substances such as PF4 or platelet-derived growth factor (PDGF). PDGF is the main source of mitogenic activity found in serum. In vitro, it induces the proliferation of smooth muscle cells (SMC) which is known to be involved in the development of atherosclerotic lesions. Atherosclerosis is one of the major complications of uremic patients undergoing chronic hemodialysis. To investigate whether this complication could be due to the dialysis itself, we measured the mitogenic activity in plasma of 10 patients undergoing hemodialysis on cuprophane membrane, using human arterial SMC in culture. Mitogenic activity in plasma increased about 3-fold during dialysis. These results may provide an argument in favor of a contribution of platelet activation and release of mitogenic activity to atherosclerosis in patients dialysed with cuprophane membranes.

Association between sympathetic activity and the atherogenic serum cholesterol fraction

SummaryA possible modulating influence of nor-adrenergic activity on serum lipoproteins was assessed under placebo conditions and following 4 weeks of sympathetic neurone blockade with debrisoquine in 9 normal subjects, 11 patients with mild essential hypertension, 9 normotensive, and 9 hypertensive hemodialysis patients. Plasma nor-epinephrine (NE) did not differ significantly among groups on placebo and was consistently reduced (P<0.05−0.001) by sympathetic blockade. The latter also decreased (P<0.05−0.001) plasma total cholesterol (C) as well as low and very low density lipoprotein cholesterol (LDL + VLDL-C) in the three patient groups. In the two dialysis groups, basal levels of plasma triglycerides (Tg) were increased and high density lipoprotein cholesterol (HDL-C) was diminished (P<0.01−0.001); sympathetic blockade lowered Tg and raised HDL-C (P<0.01−0.001). In normal subjects, sympathetic blockade did not significantly modify plasma lipoproteins. In the three patient groups, significant correlations (r=0.62–0.88;P<0.05–< 0.001) existed between (a) basal plasma NE and total C or LDL + VLDL-C and (b) debrisoquineinduced changes in NE and changes in total LDL + VLDL-C. These findings suggest that in essential hypertension as well as in hemodialysis patients, the atherogenic C fraction, represented by LDL + VLDL-C, may be modulated by the nor-adrenergic activity.

Hypertensive Dysregulation and Its Modification by Calcium Channel Blockade in Nonoliguric Renal Failure

UNLABELLED To investigate the pathogenetic constellation and its modification by calcium channel blockade in hypertension associated with chronic nonoliguric renal failure, blood pressure (BP), various pressor factors or correlates, cardiovascular responsiveness, and plasma atrial natriuretic peptide (ANP) were assessed in 15 hypertensive patients (serum creatinine 160-715 mumol/l) before and after 6 weeks of intervention with the agent nitrendipine. On placebo, these patients had a lower plasma angiotensin II (AngII) clearance and higher values of supine plasma AngII, aldosterone, norepinephrine (NE), and heart rate than healthy humans. Acute responses of BP to AngII and of heart rate to isoproterenol were blunted in the patients (p less than 0.05-0.001). Plasma ANP was elevated, correlated positively with systolic BP, and rose in response to NE pressor infusion (p less than 0.05-0.001). Exchangeable sodium and blood volume did not differ significantly from normal values. Nitrendipine reduced the cardiovascular responses to AngII, NE, and isoproterenol and lowered supine BP from 173/102 +/- 5/2 to 146/81 +/- 3/3 mm Hg and upright BP from 170/105 +/- 5/2 to 145/86 +/- 4/3 mm Hg (p less than 0.05-0.001); except for slightly increased plasma AngII, the levels of other endocrine variables, exchangeable sodium, blood volume, and creatinine clearance were not significantly modified. CONCLUSIONS Hypertension accompanying chronic nonoliguric renal impairment seems to be strongly AngII and probably also NE dependent. Circulating ANP levels are high in this setting. Calcium channel blockade with nitrendipine effectively reduces cardiovascular AngII and NE dependence and BP.