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Communications to the Editor |

The Loss of Endothelium-Dependent Vascular Tone Control in Systemic Sclerosis FREE TO VIEW

Riccardo Livi, MD, PhD; Laila Teghini, MD; Sergio Generini, MD, PhD; Marco Matucci-Cerinic, MD, PhD
Author and Funding Information

University of Florence Florence, Italy

Correspondence to: Riccardo Livi, MD, PhD, Department of Internal Medicine, Section of Rheumatology and Nephrology, Viale Pieraccini, 18–50139 Firenze, Italy; e-mail: rlivi@unifi.it



Chest. 2001;119(2):672-673. doi:10.1378/chest.119.2.672
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To the Editor:

Systemic sclerosis (SSc) is characterized by the widespread involvement of the microvasculature and by severe damage to the endothelium1as well as by the modification of vascular tone control.2 The endothelium-dependent control of vascular tone is one of the main functions that is jeopardized during endothelial injury.

The work of Cailes et al3is a precious report showing the impairment of the endothelium-dependent control of the vascular tone in the lungs of SSc patients. Actually, our group was the first to report in 1990 such a result in the acral circulation of patients with SSc. We demonstrated that during the evolution of the disease, the endothelium-dependent vasodilation was impaired either when the level of von Willebrand factor, the marker of endothelial injury, was normal in the early phase of the disease or when it was greatly raised in the advanced phase of the disease.4The failure of endothelial-dependent regulation of vasodilation then was confirmed in the acral circulation by Bedarida et al5and in the skin circulation by La Civita et al.6

Recent data indirectly also demonstrate a defective vasodilating ability in the renal vasculature of SSc patients who have no sign of kidney involvement during standard clinical evaluations.7 In fact, we have found that the renal functional reserve, or the ability of the kidney to increase its glomerular filtration rate (GFR) and effective plasma flow (ERPF) when challenged with a protein or an amino acid load is blunted in patients with SSc. During the amino acid load test, GFR, ERPF, and total renal vascular resistance (TRVR) remained substantially unchanged in 20 SSc patients ([mean± SD] GFR, −2 ± 13.1 mL/min; ERPF, −4.1 ± 62.5 mL/min; and TRVR, 662 ± 2,215 dyne · s−1 · cm−5), whereas 10 healthy control subjects showed the expected significant changes in these parameters (GFR, 30.0 ± 13.3 mL/min[ p < 0.001]; ERPF, 111.6 ± 39.6 mL/min [p < 0.001]; TRVR, −1,659 ± 559 dyne · s−1 · cm−5[ p < 0.004]). Only five of 20 SSc patients had a GFR increase comparable to that of the control subjects (≥ 10%). The defective response was not dependent on the duration or the clinical subset of the disease, and it could be observed early in the course of the illness (median time interval from diagnosis, 18 months).

There is general agreement that the activation of the renal functional reserve depends on preglomerular vasodilation, and nitric oxide has been indicated as a major mediator of the phenomenon. Thus, the defective renal functional response to the protein load reflects an impaired endothelial-dependent vasodilation in the renal vasculature.7

In conclusion, the analysis of the literature of the last decade shows that in SSc, the endothelium-dependent control of the vascular tone is profoundly deranged in different organs. This evidence strongly suggests that the pivotal aim of the physician, in particular in the early phase of the disease, is the protection of the endothelium in order to keep its function at a steady level. This might allow an adequate tissular blood flow, thus avoiding the damage due to ischemia and reperfusion, as well as the further breakdown of vessel patency.

References

Matucci Cerinic, M, Kahaleh, BM, LeRoy, EC (1995) The vascular involvement in systemic sclerosis. Furst, D Clements, P eds.Systemic sclerosis,153-174 Lea and Febiger. Philadelphia, PA:
 
Matucci Cerinic, M, Generini, S, Pignone, A New approaches to Raynaud’s phenomenonCurr Opin Rheumatol1997;544,9-14
 
Cailes, J, Winter, S, Du Bois, RM, et al Defective endothelially mediated pulmonary vasodilation in systemic sclerosis.Chest1998;114,178-184. [CrossRef] [PubMed]
 
Matucci Cerinic, M, Pietrini, U, Marabini, S Local venomotor response to intravenous infusion of substance P and glyceryl trinitrate in systemic sclerosis.Clin Exp Rheumatol1990;8,561-564. [PubMed]
 
Bedarida, G, Kim, D, Blaschke, TF, et al Venodilation in Raynaud’s disease.Lancet1993;342,1451-1454. [CrossRef] [PubMed]
 
La Civita, L, Rossi, M, Vagheggini, G, et al Microvascular involvement in systemic sclerosis: laser Doppler evaluation of reactivity to acetylcholine and sodium nitroprusside by iontophoresisAnn Rheum Dis1998;57,52-55. [CrossRef] [PubMed]
 
Livi R, Teghini L, Pignone A, et al. Renal functional reserve is impaired in patients with systemic sclerosis without clinical signs of kidney involvement. 2000 Ann Rheum Dis (in press).
 

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References

Matucci Cerinic, M, Kahaleh, BM, LeRoy, EC (1995) The vascular involvement in systemic sclerosis. Furst, D Clements, P eds.Systemic sclerosis,153-174 Lea and Febiger. Philadelphia, PA:
 
Matucci Cerinic, M, Generini, S, Pignone, A New approaches to Raynaud’s phenomenonCurr Opin Rheumatol1997;544,9-14
 
Cailes, J, Winter, S, Du Bois, RM, et al Defective endothelially mediated pulmonary vasodilation in systemic sclerosis.Chest1998;114,178-184. [CrossRef] [PubMed]
 
Matucci Cerinic, M, Pietrini, U, Marabini, S Local venomotor response to intravenous infusion of substance P and glyceryl trinitrate in systemic sclerosis.Clin Exp Rheumatol1990;8,561-564. [PubMed]
 
Bedarida, G, Kim, D, Blaschke, TF, et al Venodilation in Raynaud’s disease.Lancet1993;342,1451-1454. [CrossRef] [PubMed]
 
La Civita, L, Rossi, M, Vagheggini, G, et al Microvascular involvement in systemic sclerosis: laser Doppler evaluation of reactivity to acetylcholine and sodium nitroprusside by iontophoresisAnn Rheum Dis1998;57,52-55. [CrossRef] [PubMed]
 
Livi R, Teghini L, Pignone A, et al. Renal functional reserve is impaired in patients with systemic sclerosis without clinical signs of kidney involvement. 2000 Ann Rheum Dis (in press).
 
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