Cyclosporine-Induced Sympathetic Activation and Hypertension after Heart Transplantation

Scherrer, Urs; Vissing, Susanne; Morgan, Barbara J.; Rollins, Julia A.; Tindall, Richard S. A.; Ring, S.; Hanson, Peter; Mohanty, Pramod K.; Victor, Ronald G.

doi:10.1056/nejm199009133231101

Cited by 401 publications

(165 citation statements)

References 32 publications

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“…It is important to note that this functional abnormality is also observed in patients with cirrhosis, whose hemodynamic characteristics are extremely different from those found in OLT patients. 12 This result is in contrast to previous studies in conductance arteries or in renal microvessels from CsA-pretreated rats, 7,24 and in human heart transplant recipients, 2 indicating that the CsA-induced hypertension could be associated with an exaggerated response of resistance vessels to the pressor stimuli. On the contrary, our observations are in keeping with recent reports that have also observed attenuated response to pressor stimuli in rats that received CsA.…”

Section: Discussioncontrasting

confidence: 75%

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Selective impairment of endothelium-mediated vasodilation in liver transplant recipients with cyclosporin A -induced hypertension

et al. 1998

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Arterial hypertension is commonly observed in orthotopic liver transplantation (OLT) recipients receiving cyclosporin A (CsA), but the precise pathogenetic mechanisms remain partially unknown. The aim of this study was to investigate endothelium-dependent and -independent dilation and adrenergic constriction of resistance vessels of OLT recipients treated with CsA. Vascular reactivity was examined in 22 OLT patients, 10 with and 12 without arterial hypertension, and in 10 control subjects by assessing the forearm blood flow response to the brachial artery infusion of increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine. In 10 OLT patients, the response to methacholine was also examined after acetylsalicylate. The ratio of serum nitrite and nitrate to serum creatinine was lower (P F .05) in OLT patients with hypertension than in nonhypertensive patients and controls. Basal forearm flow was similar in the three groups. Methacholine vasodilation was impaired in the hypertensive patients as shown by a lower maximum forearm vasodilator response and a shift in the dose response curve to methacholine to the right compared with the nonhypertensive OLT patients and the controls. The response to methacholine was not modified after salicylate. Forearm flow response to nitroprusside was similar in the three groups. No differences between the patients and the controls were found in the maximum forearm flow contraction in response to phenylephrine. An impairment in endothelium-dependent vasodilation could mediate arterial hypertension in OLT patients immunosuppressed with CsA. (HEPATOLOGY 1998;27:332-338.)Arterial hypertension is a side-effect commonly observed in patients with an allogeneic solid organ graft receiving an immunosuppressive regimen based on cyclosporin A (CsA). 1,2 Published reports show that between 60% and 85% of transplant recipients treated with CsA develop hypertension. 3 The precise pathogenetic pathways underlying CsA-induced hypertension remain partially unknown. This problem is further hindered by the frequent discrepancy between the results obtained in humans and in animal models, and the relative resistance of rats that receive CsA to develop systemic hypertension. These facts make it difficult to extrapolate data from the experimental to the human setting. 4 Recent lines of evidence point to a disturbance in the local mechanisms of vascular regulation as the most likely cause of hypertension after transplantation. In this regard, several studies that have focused on the effects of CsA on arachidonic acid metabolites and endothelium-dependent and -independent vasodilation suggest that the arterial hypertension developed during CsA therapy reflects a shift in favor of vasoconstriction through an impairment of vasodilating mechanisms. [5][6][7][8][9][10][11] These studies have been performed in animal models, in vessels from healthy humans incubated with CsA, or in vessels from CsA-treated patients. However, no study to date has investigated the pattern of reacti...

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Section: Discussioncontrasting

confidence: 75%

“…1,2 Published reports show that between 60% and 85% of transplant recipients treated with CsA develop hypertension. 3 The precise pathogenetic pathways underlying CsA-induced hypertension remain partially unknown.…”

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confidence: 99%

Selective impairment of endothelium-mediated vasodilation in liver transplant recipients with cyclosporin A -induced hypertension

et al. 1998

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“…28 Vessel wall properties may be affected by sympathetic overactivity which can be observed in cyclosporine treated patients. 29 Moreover, the effects of cyclosporine on the vessel wall function may also be related to structural modifications. Cyclosporine can increase thromboxane excretion.…”

Section: Discussionmentioning

confidence: 99%

A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients

et al. 1998

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The mechanisms responsible for reduced arterial distensibility in renal transplant recipients remain to be evaluated. The present longitudinal study was aimed to evaluate the effect of hypertension on the evolution of vessel wall properties in renal transplant recipients. The mechanical properties of the common carotid artery were determined in 24 normotensive and 24 treated hypertensive renal transplant recipients 6-12 weeks after transplantation. The measurements were repeated after 2 years. Arterial distension was determined by using a multigate pulsed Doppler system, blood pressure (BP) was measured by a mercury sphygmomanometer. BP was 127 ؎ 3/80 ؎ 2 mm Hg at entry and 133 ؎ 3/82 ؎ 2 mm Hg after 2 years in the normotensive group, 146 ؎ 4/90 ؎ 3 mm Hg at entry and 145 ؎ 3/87 ؎ 2 mm Hg after 2 years in the hypertensive group (P Ͻ 0.01, normotensives vs hypertensives). The distens-

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“…It could be related either to a lower clearance of prorenin or to a dysregulation at the level of gene transcription, as suggested by Kahan,40 and/or to partial blockade in the intrarenal conversion of inactive to active renin. 41 A third mechanism involved in RAS stimulation by cyclosporin is sympathetic stimulation, which has been suggested by early experiments in rats 42 and was confirmed by Scherrer in humans 43 with striking increases in sympathetic nerve activity and in peripheral vascular resistances in cardiac transplant recipients under cyclosporin with consequent direct stimulation of the RAS.…”

Section: Introductionmentioning

confidence: 91%

Effects of transplantation on the renin angiotensin system (RAS)

Farge

Julien

1998

J Hum Hypertens

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Hypertension in organ transplant recipients is associated with several functional modifications of the renin angiotensin system (RAS), which varies according to the type of transplanted organs (kidney, heart, liver or bone marrow) and the immunosuppressive regimen. Before transplantation, chronic organ failure is associated with direct and indirect stimulation of both systemic and local RASs. After transplantation, cyclosporin per se is the major determinant of hypertension. It induces

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Cyclosporine-Induced Sympathetic Activation and Hypertension after Heart Transplantation

Abstract: Cyclosporine-induced hypertension is associated with sympathetic neural activation, which may be accentuated by the cardiac denervation that results from heart transplantation.

Cited by 401 publications

References 32 publications

Selective impairment of endothelium-mediated vasodilation in liver transplant recipients with cyclosporin A -induced hypertension

Selective impairment of endothelium-mediated vasodilation in liver transplant recipients with cyclosporin A -induced hypertension

A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients

Effects of transplantation on the renin angiotensin system (RAS)

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