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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 289; no. 6; pp. R1580 - R1588
• Main Authors: Pladys, P, Sennlaub, F, Brault, S, Checchin, D, Lahaie, I, Le, N. L. O, Bibeau, K, Cambonie, G, Abran, D, Brochu, M, Thibault, G, Hardy, P, Chemtob, S, Nuyt, A. M
• Format: Journal Article
• Language: English
• Published: United States 01.12.2005
• Subjects: Animals; Diet, Protein-Restricted - adverse effects; Disease Susceptibility - embryology; Disease Susceptibility - pathology; Disease Susceptibility - physiopathology; Female; Hypertension - embryology; Hypertension - etiology; Hypertension - pathology; Hypertension - physiopathology; Male; Microcirculation - pathology; Microcirculation - physiopathology; Neovascularization, Pathologic - embryology; Neovascularization, Pathologic - pathology; Neovascularization, Pathologic - physiopathology; Pregnancy; Prenatal Exposure Delayed Effects - pathology; Prenatal Exposure Delayed Effects - physiopathology; Rats; Rats, Wistar; Vascular Diseases - embryology; Vascular Diseases - etiology; Vascular Diseases - pathology; Vascular Diseases - physiopathology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00031.2005

Research Center, Hôpital Sainte-Justine, Department of 1 Pediatrics, 2 Pharmacology and 3 Obstetrics, Université de Montréal, Canada; and 4 Institut de Recherches Cliniques de Montréal, Montreal, Canada Submitted 18 January 2005 ; accepted in final form 14 July 2005 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. microvascular rarefaction; angiotensin; nitric oxide Address for reprint requests and other correspondence: Anne Monique Nuyt, Research Center, Hôpital Sainte-Justine, Dept. of Pediatrics, Univ. of Montreal, 3175 Côte Sainte-Catherine, Montreal, Quebec, Canada, H3T 1C5 (e-mail: anne-monique.nuyt{at}recherche-ste-justine.qc.ca )