Differential effects of cyclosporine and tacrolimus on arterial function

Abstract

Summary Cardiovascular complications are the leading cause of death in renal transplant recipients and constitute one of the leading causes of graft failure. Calcineurin inhibitors (CNI) induce an acceleration of atherosclerotic processes in the arterial wall. There are conflicting data whether cyclosporine A (CsA) and tacrolimus (Tac) differ in their deleterious effects on arterial stiffening. The present study combines several measurement techniques to provide a global and reliable assessment of the differential effects of CNI on the gold‐standard parameters of arterial function. Pulse wave analysis was performed by the SphygmoCor (AtCor®), HEM‐9000AI (Omron®), and CR‐2000 device (Hypertension Diagnostics®) in 56 stable renal transplant recipients (29 CsA, 27 Tac). Groups were homogeneous for age, gender, body mass index, time on dialysis prior to transplantation, and graft function. Whereas systolic and diastolic blood pressure, central aortic blood pressure, cardiac index, large and small artery compliance index (C1 and C2), and pulse wave velocity did not significantly differ between CsA and Tac, augmentation index (AI75) was significantly lower in patients treated with Tac. This finding was consistent as assessed by two different measurement systems (P < 0.05). Compared to CsA, Tac has a favorable impact on augmentation index, a strong independent predictor for cardiovascular mortality.

Assessments of Arterial Stiffness and Endothelial Function Using Pulse Wave Analysis

“…A number of commercial devices are available to automate PWA assessments, including Compilor (tonometric device) [44, 45], Sphygmocor (tonometric device) [44, 46–49], PulsePen (tonometric device) [50, 51], ARCSolver [47, 52] (oscillometric device), Arteriograph [33, 53–57] (oscillometric device), Omron (oscillometric device) [55, 58], PulseCore [59, 60] (oscillometric device), Viscorder [32, 34, 49] (oscillometric device), and PulseTrace [6, 42, 48, 61] (photoplethysmographic device). Applanation tonometry is considered the “gold standard” and is the most widely used technique [62].…”

ComparativeIn VitroEffects of Calcineurin Inhibitors on Functional Vascular Relaxations of Both Rat Thoracic and Abdominal Aorta

“…Hypertension developed in about 80%–90% of patients those are receiving CsA compared to a relatively lower (50%–60%) incidence of hypertension in patients receiving Tac treatment [14–16]. Another recent report has also shown that Tac showed a significantly lower score ( P < 0.05) than CsA when augmentation of arterial stiffening and small and large artery compliance index were considered following CsA and Tac treatment in renal transplant recipients receiving these two agents [17]. The significance of our present functional in vitro study is discussed in the light of the above clinical observations.…”

“…A number of different mechanisms have been proposed for the development of hypertension such as (i) impaired endothelium-dependent vasodilatation due to decreased generation of NO from the endothelium, (ii) increased production of vasoconstrictor peptide, ET-1, from the endothelium, (iii) endothelium-independent enhanced vasoconstriction at the level of vascular smooth muscle, (iv) increased renal vasoconstriction, (v) elevated sympathetic drive followed by activation of renin-angiotensin system leading to oxidative stress and the accompanying vasoconstriction, and (vi) defects in renal sodium handling resulting in sodium retention [17]. Although all of these mechanisms could contribute to elevation in blood pressure, earlier studies have proposed that CNIs exert direct vascular effects apart from its effects on the kidney [17]. Earlier studies with both CNIs have proposed that they could regulate endothelium-dependent as well as endothelium-independent vasodilatation [4–11].…”

A spontaneous coronary arterial dissection associated with a calcineurin inhibitor: Figure 1

“…They have been shown to be a potent vasoconstrictor by altering the levels of the vasodilator nitric oxide and the vasoconstrictor endothelin 9. Other proposed mechanisms of vascular pathology are increased production of reactive oxygen species,10 increased sympathetic tone11 and change in balance between proinflammatory and anti-inflammatory cytokines 12–14…”

“…Tacrolimus has been shown to be less aggravating to the vasculature by causing less inflammation and having fewer effects on vasoactive substances 9 11 15 16…”