Impaired retrograde transmission of vasodilatory signals via the endothelium in pre-eclampsia: a cause of reduced tissue blood flow?

Abstract

There is evidence that tissue blood flow is regulated by retrograde transmission of signals initiated at capillary and post-capillary sites, and transmitted via the endothelium to modulate pre-capillary resistance. We have used pre-eclampsia as a model to test the hypothesis that normal endothelium is required to enable adjustment of blood flow to match tissue requirements. Integrity of the endothelial pathway was assessed by measuring calf blood flow at increasing venous pressures, using an established small cumulative-step venous-congestion plethysmography protocol in ten women with pre-eclampsia, 17 normal pregnant controls and ten non-pregnant women. Endothelial cell activation was assessed by measuring plasma levels of the cell adhesion molecules, intercellular cell-adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1) and E-selectin. Baseline calf blood flow was significantly lower in pre-eclampsia than in the other two groups (P<0.0001; ANOVA). In the pre-eclampsia group, there was a fall in blood flow as venous congestion pressure was raised (P<0.0001; ANOVA). No such change was observed in the other two groups. A significant inverse correlation was observed between the reduction in blood flow in pre-eclampsia and the levels of E-selectin (r=-0.92, P=0.0002), VCAM-1 (r=-0.93, P=0.0008) and ICAM-1 (r=-0.86, P=0.001). The differences between the pre-eclamptic women and the other two groups support the notion that the failure to sustain blood flow during a cumulative pressure step protocol in the pre-eclamptic group might be influenced by interference with the retrograde transmission of signals via the endothelium in these patients.

Functional Dilator Capacity is Independently Associated with Insulin Sensitivity and Age in Central Obesity and is not Improved by High Dose Statin Treatment

“…This finding may be attributable to tissue or species differences, or to differences in signal processing. Our assessment of the integrity of signaling pathways in the skeletal muscle microvascular bed by plethysmography is also supportive of marked changes in integrated signaling mechanisms in individuals with central obesity, greater that those seen in other patient groups [2] and similarly aged healthy individuals (Gamble J., unpublished data).…”

“…Qa rest was 3.28 [2.49] mL/min/100 mL ( n = 35). Dotted line represents physiological response measured in healthy controls [2]. Data are mean ± SEM ( n = 35).…”

Evaluation of the Time Course of Vascular Responses to Venous Congestion in the Human Lower Limb

“…Based on this work, Gamble [28, 29] proposed veni-arteriolar communication in the regulation of calf arterial flow to involve dilator signals, possibly transmitted via the endothelium, that counteract the reduction in perfusion pressure during venous congestion by decreasing pre-capillary resistance. Involvement of an endothelial pathway was supported by the fact that blood flow was not maintained during cumulative venous congestion in the calves of women with pre-eclampsia and endothelial dysfunction, in association with raised levels of adhesion molecules [30]. …”

Mikrozirkulatorisches Monitoring der Sepsis

“…Die Au to ren füh ren dies auf eine re tro gra de Sig nal transduk ti on von der ve nö sen Sei te des mi krovas ku lä ren Ge fäß betts zu prä ka pil lä ren Arte rio len zu rück, mit dem Ziel, den nu tri tiven Blut fluss kon stant zu hal ten. Bei Pa tien tin nen, die un ter ei ner Prä e klamp sie leiden, ei nem Krank heits bild, bei dem es zu Stö run gen der mi kro vas ku lä ren Endo thelzell funk ti on kommt, konn ten Anim-Nyame et al eine sig ni fi kan te Re duk ti on des mi kro vas ku lä ren Blut flus ses wäh rend dieses VKP-Pro to kolls nach wei sen und zeigen, dass das Aus maß die ser Per fu si onsstö rung mit Mar kern ei nes Endo thel zellscha dens [ICAM-1, "vas cu lar cell ad he sion mo le cu le-(VCAM-)1 und E-Se lec tin] kor re liert [4]. Mög li cher wei se kann mit die sem Un ter su chungs pro to koll auch bei sep ti schen Pa ti en ten der Grad der Endothel zell dys funk ti on be stimmt wer den.…”