Microvascular rarefaction and decreased angiogenesis in rats with fetal programming of hypertension associated with exposure to a low-protein diet in utero

Abstract

In hypertension, increased peripheral vascular resistance results from vascular dysfunction with or without structural changes (vessel wall remodeling and/or microvascular rarefaction). Humans with lower birth weight exhibit evidence of vascular dysfunction. The current studies were undertaken to investigate whether in utero programming of hypertension is associated with in vivo altered response and/or abnormal vascular structure. Offspring of Wistar dams fed a normal (CTRL) or low (LP)-protein diet during gestation were studied. Mean arterial blood pressure response to ANG II was significantly increased, and depressor response to sodium nitroprusside (SNP) infusions significantly decreased in male LP adult offspring relative to CTRL. No arterial remodeling was observed in male LP compared with CTRL offspring. Capillary and arteriolar density was significantly decreased in striated muscles from LP offspring at 7 and 28 days of life but was not different in late fetal life [day 21 of gestation (E21)]. Angiogenic potential of aortic rings from LP newborn (day of birth, P0) was significantly decreased. Striated muscle expressions (Western blots) of ANG II AT(1) receptor subtype, endothelial nitric oxide synthase, angiopoietin 1 and 2, Tie 2 receptor, vascular endothelial growth factor and receptor, and platelet-derived growth factor C at E21 and P7 were unaltered by antenatal diet exposure. In conclusion, blood pressure responses to ANG II and SNP are altered, and microvascular structural changes prevail in this model of fetal programming of hypertension. The capillary rarefaction is absent in the fetus and appears in the neonatal period, in association with decreased angiogenic potential. The study suggests that intrauterine protein restriction increases susceptibility to postnatal factors resulting in microvascular rarefaction, which could represent a primary event in the genesis of hypertension.

Cardiovascular disease and weight … at birth

“…In vivo, unlike full-term controls, LBW-ECFCs were also unable to form robust capillary networks in Matrigel plugs injected in nu/nu mice, thus confirming their reduced angiogenic potential. These findings provide the first evidence of a relationship between birth weight and the angiogenic properties of ECFCs, and a potential mechanism for the microvascular rarefaction, arteriolar narrowing, and decreased branching previously described in animal models of intrauterine growth restriction 5 For personal use only. on May 12, 2018. by guest www.bloodjournal.org From infants with developmentally programmed hypertension.…”

“…In a collaborative effort between the CIBMTR and EBMT, new retrospective and prospective cohort studies are being implemented to follow patients who are being treated by autologous HSCT for AIDs. 5,6 The current study by Daikeler and colleagues creates an exceptionally useful milestone but emphasizes the need for such high-quality tracking of posttransplantation complications in this newly evolving indication for autologous HSCT. …”

Coronary Constriction to Angiotensin II Is Enhanced by Endothelial Superoxide Production in Sheep Programmed by Dexamethasone

“…Supporting the relevance of these findings, a role for renin-angiotensin system activation in programmed cardiovascular disease has now been demonstrated in studies that bridge animal models and experimental interventions (5,(7)(8)(9)(10)(11). Among its cardiovascular effects, Ang II is a prototypical agonist for vascular NADPH oxidase, an enzyme linked to progression of atherosclerotic plaques through increased endothelial superoxide production (12,13).…”

Angiogenesis and hypertension: an update

“…16 In addition, deficient embryonic vascular development, low birth weight 18 and impaired postembryonic vascular growth impede the formation of microvascular networks. 19,20 Thus, capillary rarefaction mostly predates, but can also follow sustained hypertension (Figure 1). …”