There is now substantive evidence that hypertension and cardiovascular disease may result from insults that are inflicted on the developing fetus. Prenatal glucocorticoids are frequently administered to pregnant women to accelerate pulmonary lung maturation. In preliminary data we have found that administration of dexamethasone to pregnant rats at specific times during fetal development results in hypertension when the animals were studied as adults. While previous studies have hypothesized and provided indirect evidence that there is an alteration in sodium transport, this has not been critically or directly examined. The overall goal of this proposal is to determine how prenatal insults program hypertension in later life.
We aim to determine the mechanism of the altered sodium transport by prenatal programming. In preliminary data we show that prenatal administration of dexamethasone to pregnant rats results in an increase in proximal tubule sodium transport. We plan to examine the nephron segments involved and the mechanism for this increase in tubule transport using in vitro microperfusion and in vivo micropuncture.
We aim to determine if the increased proximal tubule sodium transport by prenatal dexamethasone is via dysregulation of the proximal tubule renin- angiotensin system. We present preliminary data showing that there is an alteration in the intrarenal renin-angiotensin system by prenatal programming and will examine directly if the endogenous proximal tubule renin-angiotensin system mediates the altered sodium transport by prenatal programming in rats. In preliminary data we show that renal denervation results in a normalization of the blood pressure in rats exposed to prenatal dexamethasone, while denervation did not affect the blood pressure in control animals.
We aim to examine the mechanism for the amelioration in blood pressure by renal denervation and if this is linked to the intrarenal renin-angiotensin system. Finally, there are two widely studied models for prenatal programming of hypertension;dietary protein deprivation and maternal glucocorticoid exposure. These two models may be connected since maternal dietary protein deprivation in pregnant rats leads to lower placental 11 ?-hydroxysteroid dehydrogenase activity and potentially greater fetal exposure to maternal glucocorticoids. We will dissociate maternal dietary protein deprivation from fetal exposure to maternal glucocorticoids to determine if maternal glucocorticoid exposure is the cause for hypertension, a reduction in nephron number and altered tubular transport with maternal dietary protein deprivation.
There is now substantive evidence that hypertension and cardiovascular disease may result from insults that are inflicted on the developing fetus. Prenatal glucocorticoids are frequently administered to pregnant women to accelerate pulmonary lung maturation. We show that prenatal dexamethasone can result in the development of hypertension when administered during specific times during fetal development. This proposal aims to determine how prenatal dexamethasone causes hypertension.
|Baum, Michel (2014) The bone kidney axis. Curr Opin Pediatr 26:177-9|
|Siddique, Khurrum; Guzman, German Lozano; Gattineni, Jyothsna et al. (2014) Effect of postnatal maternal protein intake on prenatal programming of hypertension. Reprod Sci 21:1499-507|
|Mizuno, Masaki; Lozano, German; Siddique, Khurrum et al. (2014) Enalapril attenuates the exaggerated sympathetic response to physical stress in prenatally programmed hypertensive rats. Hypertension 63:324-9|
|Mizuno, Masaki; Siddique, Khurrum; Baum, Michel et al. (2013) Prenatal programming of hypertension induces sympathetic overactivity in response to physical stress. Hypertension 61:180-6|
|Cheng, Chih-Jen; Lozano, German; Baum, Michel (2012) Prenatal programming of rat cortical collecting tubule sodium transport. Am J Physiol Renal Physiol 302:F674-8|
|Gattineni, Jyothsna; Twombley, Katherine; Goetz, Regina et al. (2011) Regulation of serum 1,25(OH)2 vitamin D3 levels by fibroblast growth factor 23 is mediated by FGF receptors 3 and 4. Am J Physiol Renal Physiol 301:F371-7|
|Baum, Michel; Martin, Martin G; Booth, Ian W et al. (2011) Nucleotide sequence of the Na+/H+ exchanger-8 in patients with congenital sodium diarrhea. J Pediatr Gastroenterol Nutr 53:474-7|
|Di Sole, Francesca; Hu, Ming-Chang; Zhang, Jianning et al. (2011) The reduction of Na/H exchanger-3 protein and transcript expression in acute ischemia-reperfusion injury is mediated by extractable tissue factor(s). Kidney Int 80:822-31|
|Habib, Sabeen; Gattineni, Jyothsna; Twombley, Katherine et al. (2011) Evidence that prenatal programming of hypertension by dietary protein deprivation is mediated by fetal glucocorticoid exposure. Am J Hypertens 24:96-101|
|Huang, Chou-Long; Moe, Orson W (2011) Klotho: a novel regulator of calcium and phosphorus homeostasis. Pflugers Arch 462:185-93|
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