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NEUROHUMORAL CONTROL OF CIRCULATION AND HYPERTENSION

Effect of a perinatal high-salt diet on blood pressure control mechanisms in young Sprague-Dawley rats

¹Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah 84602; and ²Department of Pharmacology, University of Mississippi, University, Mississippi 38677

Submitted 27 August 2003 ; accepted in final form 5 January 2004

In the present investigation we sought to determine if a perinatal high-salt treatment affects blood pressure at an early age (30 days), and if so, to determine the mechanisms responsible for the hypertension. Pregnant dams were given an 8% NaCl diet [high-salt (HS) rats] during the final one-third of gestation and throughout the suckling period. After weaning, the pups continued to receive the high-salt diet until testing at age 30 days. Control groups received a normal-salt diet (NS rats). In HS rats, mean arterial pressure (MAP) was significantly increased (110 ± 5 vs. 96 ± 3 mmHg) compared with NS rats. Blockade of brain AT₁ receptors with intracerebroventricular losartan decreased MAP in HS but not NS rats. Blockade of -adrenergic receptors with intravenous phentolamine or ganglionic transmission with intravenous chlorisondamine produced a greater decrease in MAP in HS rats. Baroreflex control of heart rate was assessed using a four-parameter logistics function. The mid-range MAP (p3) was significantly increased in the HS rats. No other baroreflex parameters were affected. Specific binding of ¹²⁵I-[Sar¹,Ile⁸]ANG II to AT₁ receptors was increased in the subfornical organ (SFO) of the HS rats. Expression of AT_1a receptor mRNA was greater in both SFO and PVN of the HS rats. These data suggest that even at an early age, Sprague-Dawley rats treated with a perinatal high-salt diet are hypertensive. The elevated blood pressure appears to be caused by increased sympathetic nervous activity, resulting, in part, from increased brain AT₁ receptor activation.

AT₁ receptor; brain; subfornical organ; hypertension; sympathetic nervous system

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