Effect of soluble endoglin on endothelium-dependent vasorelaxation in rat isolated tail artery

Malvika Gulati, Arunan Sujenthiran, Sumangali Wijetunge, Alun Hughes

Imperial College London, London, UK

Endoglin (CD105) is highly expressed in endothelial cells, and also found in vascular smooth muscle cells. It acts as an accessory receptor for TGF-β and binds with high affinity to TGF-β1 and TGF-β3. Increased levels of a circulating form of endoglin (soluble endoglin) are found in pre-eclampsia and has been implicated in its pathogenesis. Soluble endoglin increases vascular permeability and increases blood pressure in vivo (Venkatesha et al., 2006). However, the acute effects of soluble endoglin on vascular reactivity and endothelial function are not clear.

Isometric tension was measured in rat isolated tail arteries mounted in a myograph containing a modified Kreb’s physiological saline solution. Arteries were bubbled with 95% O2 and 5% CO2 and maintained at 37ºC. SDS-PAGE was carried out on rat tail arterial lysates and Western blotting was performed using specific anti-eNOS antibody. Data are presented as means ± SEM. Statistical comparisons were made using ANOVA or a paired Student’s t-test. P<0.05 was considered significant.

In endothelium-intact arteries, acetylcholine (ACh) concentration-dependently relaxed the stable near maximal contraction induced by phenylephrine (10μM; PE) and this effect was inhibited by 100μM L-NMMA + 10μM oxyhaemoglobin indicating that it was dependent on release of NO. Pre-incubation with soluble endoglin (20ng/ml) for 1h, inhibited the ACh concentration-response curve (pEC50 control = 7.5±0.2, endoglin = 6.7±0.2, p = 0.005, n = 6). However soluble endoglin did not affect sodium nitroprusside (SNP)-induced relaxations. Soluble endoglin also did not affect PE-induced contractions. Pre-incubation with TGF-β1 (20ng/ml) did not have significant effects on PE-induced contraction or ACh-induced relaxation. Assessment of SDS-PAGE and Western blotting by densitometry showed that soluble endoglin did not affect the expression of total eNOS protein levels in rat tail arteries (n = 5, p = 0.9)

Soluble endoglin inhibits endothelium-dependent relaxation in rat tail artery. The mechanism involved remains to be established, but does not involve changes in expression of total eNOS protein. Endoglin-induced impairment of endothelial vasodilatation may have a role in vivo in the pathogenesis of the hypertensive state in pre-eclampsia.

Venkatesha et al., Nat Med. 2006;12:642-9