University of Kentucky

Hypertension in SHRxBN Rats

Presenter Information

Greg Todd, University of Kentucky

Institution

University of Kentucky

Abstract

Angiotensin II and salt intake play substantial roles in the regulation of arterial pressure, and are therefore major targets for the investigation and treatment of hypertension. This study examined the relationship between long term high sodium chloride (NaCl) intake and the density of angiotensin type 1 receptor (AT1r) in hypothalamic, forebrain, and renal tissues from a unique model of hypertension. A hypertensive female Spontaneously Hypertensive rat (SHR) and a normotensive Brown Norway male (BN) were crossed. Hypertensive F1 offspring were sib/sib crossed, yielding hypertensive experimental offspring. From weaning, experimental rats were raised on either a normal (0.8%; NS) or high (4%; HS) NaCl diet. Previous studies show that HS rats have a greater salt appetite, averaging 3.46 + 0.899 mmol NaCl/day, compared to 1.54 + 0.856 mmol NaCl/day ingested by NS rats. Using antibodies specific for At1r (Santa-Cruz; Primary 1:200; Secondary 1:2,000), western blot analysis indicates that hypothalamic AT1 receptor density is significantly reduced in HS rats. These data suggested that F1 sib/sib rats raised on HS decreased ability to regulate their sodium balance, due in part to decreased expression of hypothalamic AT1 receptors. To further elucidate the actions of AT1r in this model of hypertension, I am currently examining the density of AT1r in forebrain and renal tissues. This study determined the relationship between elevated lifetime sodium chloride intake and AT1r, which will further explore the impaired handling of sodium chloride in HS rats.

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Hypertension in SHRxBN Rats

Angiotensin II and salt intake play substantial roles in the regulation of arterial pressure, and are therefore major targets for the investigation and treatment of hypertension. This study examined the relationship between long term high sodium chloride (NaCl) intake and the density of angiotensin type 1 receptor (AT1r) in hypothalamic, forebrain, and renal tissues from a unique model of hypertension. A hypertensive female Spontaneously Hypertensive rat (SHR) and a normotensive Brown Norway male (BN) were crossed. Hypertensive F1 offspring were sib/sib crossed, yielding hypertensive experimental offspring. From weaning, experimental rats were raised on either a normal (0.8%; NS) or high (4%; HS) NaCl diet. Previous studies show that HS rats have a greater salt appetite, averaging 3.46 + 0.899 mmol NaCl/day, compared to 1.54 + 0.856 mmol NaCl/day ingested by NS rats. Using antibodies specific for At1r (Santa-Cruz; Primary 1:200; Secondary 1:2,000), western blot analysis indicates that hypothalamic AT1 receptor density is significantly reduced in HS rats. These data suggested that F1 sib/sib rats raised on HS decreased ability to regulate their sodium balance, due in part to decreased expression of hypothalamic AT1 receptors. To further elucidate the actions of AT1r in this model of hypertension, I am currently examining the density of AT1r in forebrain and renal tissues. This study determined the relationship between elevated lifetime sodium chloride intake and AT1r, which will further explore the impaired handling of sodium chloride in HS rats.