Abstract
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 AT1 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 AT1 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.
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Abbreviations
- ACE-I:
-
angiotensin-converting enzyme inhibitor
- AngII:
-
angiotensin II
- AP:
-
area postrema
- BPV:
-
blood pressure variability
- HR:
-
heart rate
- ICV:
-
intracerebroventricular
- MABP:
-
mean arterial blood pressure
- MEPO:
-
median preoptic nucleus
- NTS:
-
nucleus of the solitary tract
- OVLT:
-
vascular organ of the lamina terminalis
- PVH:
-
paraventricular nucleus of the hypothalamus
- RAS:
-
renin-angiotensin system
- SFO:
-
subfornical organ
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This work was supported by grants from the Canadian Institutes of Health Research and the Banting Research Foundation with matching funds from the Medical Research Council of Canada. P.P. was supported by a Institut National de Santé et Recherche Médicale (France) and the Canadian Institutes of Health Research (INSERM-CIHR) research fellowship and by the Conseil Régional de Bretagne.
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Pladys, P., Lahaie, I., Cambonie, G. et al. Role of Brain and Peripheral Angiotensin II in Hypertension and Altered Arterial Baroreflex Programmed during Fetal Life in Rat. Pediatr Res 55, 1042–1049 (2004). https://doi.org/10.1203/01.PDR.0000127012.37315.36
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DOI: https://doi.org/10.1203/01.PDR.0000127012.37315.36
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