Blunted Vascular Response to Endothelin-A Receptor Blockade in Cyclosporine-Treated Lung Transplant Recipients

Silverborn, Martin; Ambring, Anneli; Nilsson, Folke; Friberg, Peter; Jeppsson, Anders

doi:10.1016/j.healun.2004.04.010

Cited by 6 publications

(6 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests that there is an impaired forearm vasoconstrictive response to ET‐1 in hypertensive lung recipients, possibly on receptor levels. This hypothesis is supported by previous studies in transplant recipients demonstrating impaired forearm vasodilatation after selective ET‐a receptor blockade [9,20].…”

Section: Discussionsupporting

confidence: 78%

“…Whether this is a generalized effect in all vascular beds has previously been questioned by Bracht et al [11], who found lower FVR despite higher blood pressure in heart recipients late after transplantation. In addition, in two recent studies, we found no evidence of increased FVR in lung transplant recipients [9,10]. However, those latter investigations were performed in lung recipients within 18 month after transplantation and without hypertension, and it is possible that vasoconstriction and increased FVR occur later.…”

Section: Discussioncontrasting

confidence: 52%

“…It is unclear if all vascular beds contribute to the increased systemic vascular resistance. Our group and others have presented data that questions the presence of increased skeletal muscle vascular resistance in CsA treated lung and heart transplant recipients [9–11]. However, our investigations were performed relatively early after transplantation (1–18 month) in lung recipients without manifest hypertension.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Vascular resistance and endothelial function in cyclosporine-treated lung transplant recipients

et al. 2006

Self Cite

View full text Add to dashboard Cite

Summary The majority of patients undergoing solid organ transplantation develop hypertension, to which vasoconstriction and impaired endothelial function have been suggested to contribute. We compared basal vascular resistance and nitric oxide‐mediated endothelial‐dependent and independent vasoreactivity between cyclosporine‐treated lung transplant recipients and healthy subjects. Forearm blood flow was measured by venous occlusion plethysmography at rest and during acetylcholine, glyceryltrinitrate and N(G)‐monomethyl‐l‐arginine acetate (l‐NMMA) infusion in 11 lung transplant recipients 3–5 years after transplantation and in eight healthy subjects. Forearm vascular resistance (FVR) was calculated. Plasma levels of endothelin‐1 (ET‐1) and von Willebrand factor (vWf) were analysed. Basal vascular resistance was 40% lower in transplant recipients than in healthy subjects (P = 0.021). Endothelial‐dependent and independent vasodilation did not differ. Plasma levels of ET‐1 and vWf were higher in transplant recipients (P = 0.009 and P < 0.001 respectively). There was a significant correlation between ET‐1 levels and FVR in healthy subjects (r = 0.83, P = 0.042), but not in transplant recipients (r = −0.14, P = 0.70). The findings oppose the theory of generalized vasoconstriction and impaired endothelial function in the pathogenesis of hypertension after transplantation. Increased plasma levels of ET‐1 do not cause increased FVR in lung transplant recipients.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Discussioncontrasting

confidence: 52%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Vascular resistance and endothelial function in cyclosporine-treated lung transplant recipients

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…The effect of bosentan could be more significant in combination with calcineurin inhibitors, as plasma ET-1 levels are elevated in cyclosporine-treated lung transplant recipients. 30 In addition, the findings of the present study suggest the potential for the combination of ACE inhibitor plus ET-1 receptor antagonist as a further therapeutic strategy in patients with BO. Nevertheless, we acknowledge certain limitations of our animal model-namely, that it is heterotopic, development of the lesions is relatively fast, and these lesions occur not in the bronchioles, but in the trachea, which has a different anatomic structure.…”

Section: Discussionmentioning

confidence: 56%

Effects of Blockade of the Renin–Angiotensin and Endothelin Systems on Experimental Bronchiolitis Obliterans

Antus

Sebe

Fillinger

et al. 2006

The Journal of Heart and Lung Transplantation

View full text Add to dashboard Cite

“…In addition to those described here, data are emerging in a number of other areas where BP control is often a problem, eg, after transplantation. ET-1 has been implicated in the hypertensioncomplicating heart, 106 lung, 107 and kidney 108 transplants, and although animal data suggest a role for ET receptor antagonists in treating this hypertension, 109 there are currently few human data. Although unlikely to be considered as first-line treatment, ET receptor antagonists are a promising new and innovative drug class to add to the antihypertensive arma- In disease, ET-1 promotes hypertension and cardiovascular disease through a number of mechanisms.…”

Section: Perspectivesmentioning

confidence: 99%

Role of Endothelin-1 in Clinical Hypertension

et al. 2008

View full text Add to dashboard Cite

H ypertension is the most common risk factor worldwide for cardiovascular morbidity and mortality. 1,2 Currently it is estimated that a quarter of the world's adult population is hypertensive, and this number is projected to increase to Ϸ30% by 2025. 1 Although, there exist a number of drug therapies for hypertension, blood pressure (BP) control to target is still only achieved in Ϸ30% of patients. 3 Over the last 20 years, novel licensed therapies have primarily focused on the renin-angiotensin-aldosterone system. Endothelin (ET) receptor antagonism represents an innovative, but as yet only partially explored, alternative approach in the management of hypertension.A review in Hypertension 10 years ago outlined the potential role that ET-1 may play in the development of hypertension, 4 as proposed by Yanagisawa et al in their original Nature article in 1988. 5 This largely focused on preclinical data because, at that time, there was only 1 published study of ET receptor antagonism in patients with essential hypertension. 6 There were also few data that focused on the relative benefits of selective or mixed ET blockade. Finally, the lack of longer-term data on safety and tolerability for these drugs made their place in the antihypertensive armamentarium unclear. In this review we aim to answer many of these questions and outline some of the key findings in this field from the last decade. Biology of the ET SystemThe ET family consists of three 21-amino acid peptides (ET-1, ET-2, and ET-3) with powerful vasoconstrictor and pressor properties. 7 Of the 3 peptides, ET-1 is the major vascular isoform and of most importance in the cardiovascular system. 8 The gene product is the 212-amino acid prepro-ET-1. This is cleaved to big ET-1, after which an ETconverting enzyme (ECE) catalyzes the generation of the biologically active ET-1 and a C-terminal fragment.ET-1 acts by binding to 2 distinct receptors, the ET A and the ET B receptors (ET A R and ET B R). 9,10 ET receptors are expressed by a wide variety of cells and tissues. Within the vasculature, ET A R and ET B R, located on vascular smooth muscle cells, mediate the vasoconstrictor effects of ET B Rs are also found on vascular endothelial cells, where their activation results in vasodilation mediated mainly by NO. 12,13 In addition, ET B Rs have a major role in the clearance of circulating ET-1. The plasma half-life of ET-1 in health is Ϸ1 minute, 14 with removal through receptor-and nonreceptormediated mechanisms. ET-1 binds to ET B R, with subsequent ligand-receptor complex internalization and intracellular degradation accounting for the majority of clearance, particularly in the pulmonary circulation, 15 although the splanchnic and renal circulations also contribute. 16 Therefore, a reduction in ET B R number, or ET B R blockade, may reduce ET-1 clearance, increasing plasma concentrations without altering production. For this reason and, importantly, because most ET-1 is released albuminally, plasma concentrations of ET-1 do not accurately reflect ET-1 productio...

show abstract

Blunted Vascular Response to Endothelin-A Receptor Blockade in Cyclosporine-Treated Lung Transplant Recipients

Cited by 6 publications

References 24 publications

Vascular resistance and endothelial function in cyclosporine-treated lung transplant recipients

Vascular resistance and endothelial function in cyclosporine-treated lung transplant recipients

Effects of Blockade of the Renin–Angiotensin and Endothelin Systems on Experimental Bronchiolitis Obliterans

Role of Endothelin-1 in Clinical Hypertension

Contact Info

Product

Resources

About