The aim of this proposal is to test that high dietary NaCl exposure alters arterial and cardiopulmonary baroreflex sensitivity secondary to changes within the anterior hypothalamic area (AHA) in NaCl-sensitive animals. These studies will employ the NaCl-sensitive spontaneously hypertensive rat of the Okamoto strain SHR-S, in which blood pressure (BP) does not increase in response to diets high in NaCl, and the normotensive NaCl-resistant Wistar-Kyoto rat (WKY) and Sprague-Dawley rat (SD).
Specific Aim #1 will test the hypothesis that high dietary NaCl exposure increases arterial and cardiopulmonary baroreflex mediated control of LSNA while decreasing arterial and cardiopulmonary baroreflex mediated control of heart rate (HR) in SHR-S, WKY, and SD rats before and after high dietary NaCl exposure.
Specific Aim #2 will test the hypothesis that blunting of arterial baroreflex mediated control of LSNA in SHR-S on a normal NaCl diet is centrally mediated. LSNA, BP, and HR responses to graded stimulation of the aortic depressor nerve will be compared in SHR-S. SHR-R, WKY, and SD rats on a normal NaCl diet. In a second experiment, aortic depressor nerve activity during graded increases in BP will be compared in the 4 rat strains on a normal NaCl diet.
Specific Aim #3 will test the hypothesis that high dietary NaCl exposure increases arterial baroreflex mediated control of LSNA in SHR-S through aa central mechanism. LSNA, BP, and HR responses to graded stimulation of the aortic depressor nerve will be compared in SHR-S, SHR-R, WKY, and SD rats before and after high dietary NaCl exposure. In a second experiment, aortic depressor nerve activity will be compared in the 4 rat strains before and after high dietary NaCl exposure.
Specific Aim #4 will test the hypothesis that AHA ablation increases arterial and cardiopulmonary baroreflex mediated control of LSNA while decreasing arterial and cardiopulmonary baroreflex mediated control of HR in SHR-S. LSNA and HR responses to acute changes in BP and blood volume in AHA and sham lesioned SHR-S, SHR-R, WKY, and SD rats on a normal NaCl diet will be compared.
Specific Aim #5 will test the hypothesis that bilateral AHA ablation results in no additional changes in arterial baroreflex sensitivity beyond those secondary to NaCl exposure. LSNA and HR responses to acute increases in BP in AHA lesioned SHR-S, SHR-R, WKY, and SD rats will be compared before and after dietary NaCl exposure. By evaluating baroreflex responses to high NaCl exposure, these studies will further our understanding of the mechanism of NaCl-sensitive hypertension.
| Calhoun, D A; Mutinga, M L (1997) Race, family history of hypertension, and sympathetic response to cold pressor testing. Blood Press 6:209-13 |
