Whole‐body cooling increases plasma endothelin‐1 levels in women with primary Raynaud's phenomenon

Abstract

To understand better the role of endothelin-1 (ET-1) in the pathogenesis of primary Raynaud's phenomenon (PRP), we investigated the basal ET-1 plasma levels and changes after whole-body cooling in healthy women and those with PRP. The study was performed as an open parallel-group comparison during the month of February. The Raynaud group included 21 female patients (mean age 45.3 years, range 21-57 years) who had had disabling Raynaud's phenomenon for a mean period of 17 years (range 2-26 years). The control group consisted of 25 healthy women (mean age 43.6 years, range 27-56 years). Plasma levels of ET-1 were measured on two separate occasions: once after 30 min of rest at room temperature and after 40 min of whole-body cooling. There were no significant differences in baseline plasma ET-1 levels between the two groups of women. The plasma ET-1 levels increased significantly in the PRP group after cold exposure (mean difference 0.11 pmol l-1, 95% CI 0.005-0.214, P = 0.012). In contrast, the levels of plasma ET-1 in the control group did not change significantly after cold provocation. In conclusion, no differences in plasma basal levels of ET-1 were observed between the two groups. However, women suffering from Raynaud's phenomenon responded with a slight but significant elevation in plasma levels of ET-1 after whole-body cooling, whereas the healthy control subjects did not. The results from the present study confirm previous observations that endothelial dysfunction may be of aetiological importance in PRP.

Cardiovascular responses to cold exposure

“…However, chronic exposure to cold did not alter plasma levels of ET-1. This is in contrast with acute cold exposure (minutes or hours) which increases plasma ET-1 levels (59,60). It should be emphasized that ET-1 is produced in endothelial cells and predominantly secreted toward the adjacent VSMC, supporting the notion that ET-1 is an autocrine/paracrine agent rather than a circulating hormone.…”

Raynaud’s phenomenon: Epidemiology and risk factors

“…Leppert et al [53] found that women with RP had increased levels of endothelin-1 after whole body cooling compared with age-matched, healthy controls. In contrast, Smyth et al [54] found no difference between baseline plasma and endothelin-1 levels in subjects with RP compared with controls.…”

Air Pollution-Induced Vascular Dysfunction: Potential Role of Endothelin-1 (ET-1) System

“…A primary outcome of these mechanisms is the initiation of endothelium dysfunction, which appears central (perhaps as a result of or in combination with oxidative stress and inflammation) to further development of CVD. Evidence suggests a strong association between endothelium dysfunction and cardiovascular events, leading to high morbidity and mortality from CVD [36] as well as other disease states [37–42]. Endothelium dysfunction is characterized by an imbalance between the dilator and constrictor forces in the vasculature.…”

“…As with CVD, the vasoconstrictive effect of ET-1 is the proposed major cause of these conditions. In the extremities, cold-temperature-induced increases in ET-1 contribute to the pathogenesis of Raynaud's phenomenon [37, 100], in which exaggerated vasoconstriction causes discomfort (ischemic pain) and discoloration of the affected areas. Likewise, ET-1-related vascular dysfunction in the eye leads to intraocular inflammation; this plays an important part in the development of primary open-angle glaucoma [41].…”