Relationship between cardiovascular hypertrophy and cardiac baroreflex function in spontaneously hypertensive and stroke-prone rats

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Objective:To determine whether the reduced baroreceptor-heart rate reflex sensitivity in genetically hypertensive rats is related to the level of cardiac or vascular hypertrophy.Design:Young spontaneously hypertensive rats (SHR), stroke-prone hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were treated chronically with the angiotensin converting enzyme (ACE) inhibitor perindopril in different regimens in order to produce a wide-ranging combination of cardiac and vascular hypertrophy.Methods:All strains were treated with perindopril (0.1, 0.3, 1 or 3 mg/kg per day) in their drinking water from 4 until 9 weeks of age. Additional groups of SHR were treated with perindopril (3 mg/kg per day) from 4 until 12 weeks and from 4 until 14 weeks of age. At 13 weeks of age all animals were chronically instrumented with arterial and venous catheters. One week later, steady-state sigmoidal mean arterial pressure-heart rate reflex curves were obtained in the conscious rats by the injection of pressor and depressor agents before and after the administration of atenolol (1 mg/kg, intravenously) to determine the vagal component. The minimum and the maximum blood pressure produced by nitroprusside and methoxamine, respectively, after simultaneous ganglion and p-adrenoceptor blockade were used as an index of whole body vascular hypertrophy. The left ventricular to body weight ratio was measured at the end of the experiment.Results:At 14 weeks of age, mean arterial pressure, the maximum and minimum autonomically blocked blood pressure and the left ventricular to body weight ratio were 34, 20, 9 and 17% higher, respectively, in SHR, and 56, 35, 27 and 39% higher, respectively, in SHRSP than in WKY rats. Perindopril treatment dose-dependently reduced both cardiac and vascular hypertrophy but to different extents. The highest doses reduced mean arterial pressure and the autonomically blocked maximum and minimum blood pressure in both hypertensive strains to the levels of untreated WKY rats but approximately 50% of the cardiac hypertrophy was still present. The left ventricular to body weight ratio was normalized in SHR only with the longer term perindopril treatments. A comparison of the baroreflex function curves in untreated SHR and SHRSP showed that the vagal component of the heart rate range was markedly reduced compared to that in WKY rats. Treated SHRSP had a normal mean arterial pressure and a normal autonomically blocked maximum and minimum blood pressure, but their vagal heart rate range was only 63% of that in WKY rats. The heart rate range in SHR treated from 4 to 9 weeks of age was only marginally greater than that of untreated SHR, despite prevention of hypertension and vascular hypertrophy. In SHR treated from 4 until 12 weeks of age, which prevented cardiac hypertrophy, the vagal heart rate range was markedly greater. With perindopril from the age of 4 to 14 weeks, the vagal baroreflex heart rate range was similar to that of WKY rats. Thus the improvement in the vagal heart rate range was more closely related to the prevention of cardiac hypertrophy (r=0.73, P< 0.001) than vascular hypertrophy or a blood pressure elevation. Since there were no further changes in the indices of hypertrophy, the presence of the ACE inhibitor was likely to have been responsible for restoring the remaining 35% of the vagal baroreflex not affected by structural factors.Conclusions:These results suggest that prevention of cardiac rather than vascular hypertrophy is the major requirement for normalizing the vagal component of the baroreceptor-heart rate reflex in hypertensive rats. However, structural changes accounted for only about two-thirds of the vagal deficit. The remainder was restored by the presence of an ACE inhibitor, suggesting that the vagal component of the baroreceptor—heart rate reflex is normally suppressed by the renin-angiotensin system

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