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Arterial Baroreflex Function And Saline Preference

Posted on:2007-04-27Degree:MasterType:Thesis
Country:ChinaCandidate:X W GuFull Text:PDF
GTID:2144360182991657Subject:Pharmacology
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INTRODUCTIONThe spontaneously hypertensive rat (SHR) was developed from Wistar Kyoto (WKY) strain exhibiting spontaneously elevated blood pressure (BP) in 1963. SHR has been widely used as an experimental model of human essential hypertension. The unusual and less explored feature of the SHR is its exaggerated preference for saline when compared to the normotensive or other genetically hypertensive strains.This behavior appears to be independent of BP per se and its precise mechanism remains unknown.Compared to normotensive strains, SHR exhibit these conspicuous features: elevated BP, increased blood pressure variability (BPV) and impaired arterial baroreflex (ABR) function. Since BP level is not a determinant in the salt preference, we speculated that the modified salt preference in SHR might be due to an impairment of baroreflex function. Furthermore, whether the relationship between baroreflex function and salt appetite was universal (also existing in normal rats)? Therefore, the present work was designed to determine the relationship between ABR function and salt preference in rats. Two experiments were completed. First, BRS (stands for ABR function) and salt preference were measured in SHR followed by an analysis to show the relationship between these two parameters. Second, salt preference was determined before and after sinoaortic denervation (SAD), which completely destroy ABR responses and markedly increase BPV without a sustained elevation of blood pressure in normotensive Sprague-Dawley (SD) rats. Besides, there is the significant correlation between ABR function and end organ damage. We also determined the end organ damage indices in SHR and wanted to explore the relationship between end organ damage and salt preference.METHODSExperiment 1Male SHR (n=27) and male WKY rats (n=10) underwent fluid-intake measurement at the age of 44-45 weeks. Having been corrected for the animal's body weight, total fluid intake (TFI;water plus saline) and saline preference (the proportion of the TFI taken as saline) were determined. Then SHR underwent catheterization under anesthesia. 48 hours later, SBP, DBP, HP and BRS were determined in the conscious state. And then the animals were killed by decapitation. The heart, aorta and right kidney were excised and rinsed in physiological saline and the gross endorgan damage indices were determined. Differences in salt preference between SHR and WKY rats were assessed by a general linear model two-way analysis of variance with time as a repeated measure. The relationships between BRS, hemodynamic variables, endorgan damage indices and saline preference were assessed by linear regression analysis.Experiment 2After fluid-intake measurements, male SD rats, aged 10 weeks, were divided into two groups: groupl for SAD, group2 for sham operation. Four weeks after SAD or sham operation, the animals underwent fluid intake measurement again. Then all the rats underwent catheterization under anesthesia. Two days later, haemodynamic parameters and BRS were determined in the conscious state. The completeness of SAD was assessed. The rats failed in SAD assessment were rejected. The differences in haemodynamic variables and BRS between SAD rats and sham-operated rats were assessed by the Student unpaired t test. Differences in salt preference between SAD rats and sham-operated rats were assessed by a general linear model two-way analysis of variance with time as a repeated measure. The Student paired t test was used to evaluate the differences in salt preference of SAD rats or sham-operated rats between before operation and after operation.RESULTSFluid intake of SHR and WKY rats offered a choice of water and saline to drinkAs expected, SHR had a significantly greater TFI [F(l,18)=5.614, p=0.029<0.05] and saline preference [F(l,18)=4.664, p=0.045<0.05] than that of WKY rats.Relationship between salt preference and BP or BRS in SHRIt was found that SHR exhibited high SBP and DBP, and a low BRS. These values are similar with those previously published by our department. In linear regression analysis, there was no significant correlation between salt preference and SBP, DBP or HP. Neither was a significant correlation found between BRS and the salt preference of SHRRelationship between salt preference and endorgan damage indices in SHRIn linear regression analysis, there was no significant correlation between salt preference and LVW/BW, RVW/BW, VW/BW, LVW/RVW, AW/length or RKW/BW.Systemic haemodynamics and BRS in SAD ratsIn SD rats 4 weeks after SAD, systolic blood pressure variability (SBPV) and diastolic blood pressure variability (DBPV) were substantially increased, with no significant change in the average levels of SBP and DBP compared with Sham controls. HP and heart period variability (HPV) remained unchanged following SAD. The BRS of SAD rats were significantly lower than that of Sham controls.Salt preference in SAD ratsThere were no differences in saline preference between the SAD rats and the Sham controls [before operation, F (1, 17) =0.489, p>0.4;after operation, F (1, 17) =0.841, p>0.3]. The saline preference of Sham controls was 32.1±4.2% (before operation) and 30.0+4.7% (after operation);and it was 28.9±1.4% (before operation) and 24.8±3.0% (after operation) in SAD rats. The saline preference was not significantly modified bySAD operation (Sham,/?>0.4;SAD,/?0.2).CONCLUSIONIt is concluded that the ABR function does not influence the salt preference in rats.
Keywords/Search Tags:baroreflex sensitivity, salt preference, sinoaortic denervation, blood pressure, spontaneously hypertensive rat, endorgan damage
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