Endoglin regulates nitric oxide‐dependent vasodilatation

Abstract

Endoglin is a membrane glycoprotein that plays an important role in cardiovascular development and angiogenesis. We examined the role of endoglin in the control of vascular tone by measuring nitric oxide (NO)-dependent vasodilation in haploinsufficient mice (Eng+/-) and their Eng+/+ littermates. The vasodilatory effect of acetylcholine, bradykinin, and sodium nitroprusside was assessed in anesthetized mice; in isolated, perfused hindlimbs; and in aortic rings. The substantial hypotensive and vasodilatory response induced by acetylcholine and bradykinin in Eng+/+ was markedly reduced in Eng+/- mice. Both kinds of animals had similar responses to sodium nitroprusside, suggesting that the deficient vasodilatory effect is not due to a NO response impairment. Urinary and plasma concentrations of nitrites, a NO metabolite, were lower in Eng+/- than in Eng+/+ mice. The levels of endothelial nitric oxide synthase (eNOS) in kidneys and femoral arteries were about half in Eng+/- than in Eng+/+ mice and were also reduced in primary cultures of aortic endothelial cells from Eng+/- compared with those from Eng+/+ mice. Furthermore, overexpression or suppression of endoglin in cultured cells induced a marked increase or decrease in the protein levels of eNOS, respectively. Thus, our results in vivo and in vitro demonstrate a relationship between endoglin and NO-dependent vasodilation mediated by the regulation of eNOS expression.

Transcriptional Factor Aryl Hydrocarbon Receptor (Ahr) Controls Cardiovascular and Respiratory Functions by Regulating the Expression of the Vav3 Proto-oncogene

“…Hemodynamic Studies-Mice were anesthetized with sodium pentobarbital and arterial pressures recorded by catheterization of the right carotid artery with a pressure probe connected to a digital data recorder (MacLab/4e, AD Instruments), as described previously (49). Recordings were subsequently analyzed with the Chart version 3.4 software (AD Instruments).…”

Targeted Genomic Disruption of H-Ras Induces Hypotension Through a NO-cGMP-PKG Pathway–Dependent Mechanism

“…Blood pressure was measured using 3 different methods: direct intraarterial measurement in anesthetized animals, 20 tail-cuff sphygmomanometer, 21,22 and radiotelemetry. 23 Blood pressure was measured under basal conditions and after the administration of the following treatments: acetylcholine (ACh) (1 g/kg body weight [BW] intraperitoneal [IP]), sodium nitroprusside (SNP) (2 g/kg BW IP), db-cGMP (5 mg/kg BW IP), N G -nitro-L-arginine methyl ester (L-NAME) (20 mg/kg BW per day, drinking water for 2 weeks), 1H- [1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ) (5 mmol/kg BW IP), DT-3 (500 g/kg BW IP), and chaetomellic acid A (1.5 mg/kg BW IP at 24 and 16 hours before blood pressure measurement and euthanasia).…”

Novel biochemical pathways of endoglin in vascular cell physiology

“…The vasoregulatory protein endothelial nitric oxide synthase (eNOS) is decreased in endoglin-deficient cells, whereas it is increased in endoglinoverexpressing cells [Jerkic et al, 2004;Toporsian et al, 2005]. At least in part, the endoglindependent increase of eNOS levels is mediated by increased stabilization of eNOS protein in caveolae, via a post-transcriptional mechanism that involves direct association of endoglin with caveolar proteins and potentially heat shock protein 90 [Toporsian et al, 2005].…”