Role of brain and peripheral angiotensin II in hypertension and altered arterial baroreflex programmed during fetal life in rat.
Intrauterine programming of hypertension is associated with evidence of increased renin-angiotensin system (RAS) activity. The current study was undertaken to investigate whether arterial baroreflex and blood pressure variability are altered in a model of in utero programming of hypertension secondary to isocaloric protein deprivation and whether activation of the RAS plays a role in this alteration. Pregnant Wistar rats were fed a normal-protein (18%) or low-protein (9%) diet during gestation, which had no effect on litter size, birth weight, or pup survival. Mean arterial blood pressure (MABP; 126 +/- 3 mm Hg 9% versus 108 +/- 4 mm Hg 18%; p < 0.05) and blood pressure variability were significantly greater in the adult offspring of the 9% protein-fed mothers. Arterial baroreflex control of heart rate, generated by graded i.v. infusion of phenylephrine and nitroprusside, was significantly shifted toward higher pressure; i.v. angiotensin-converting enzyme inhibitor normalized MABP and shifted the arterial baroreflex curve of the 9% offspring toward lower pressure without affecting the 18% offspring. For examining whether brain RAS is also involved in programming of hypertension, angiotensin-converting enzyme inhibitor and losartan (specific AT(1) receptor antagonist) were administered intracerebroventricularly; both significantly reduced MABP of the 9% but not the 18% offspring. Autoradiographic receptor binding studies demonstrated an increase in brain AT(1) expression in the subfornical organ and the vascular organ of the lamina terminalis in the 9% offspring. These data demonstrate a major tonic role of brain and peripheral RAS on hypertension associated with antenatal nutrient deprivation.
Pladys
Patrick
P
Research Center, Hôpital Sainte-Justine, Department of Pediatrics, University of Montreal, 3175 Côte Sainte-Catherine, Montreal, Quebec, Canada, H3T 1C5.
Lahaie
Isabelle
I
Cambonie
Gilles
G
Thibault
Gaétan
G
Lê
Ngoc Loan Oanh
NL
Abran
Daniel
D
Nuyt
Anne Monique
AM
D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure; D001921:Brain / Q000503:physiopathology*; D004044:Dietary Proteins / Q000008:administration & dosage; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D011247:Pregnancy; D011488:Protein Deficiency / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004044:Dietary Proteins; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D015773:Enalaprilat