The relationship between regional sympathetic activity and the onset of arterial hypertension in spontaneously hypertensive rats]

Several studies on spontaneously hypertensive rats (SHR) have demonstrated increased activity of the sympathetic nervous system (SNS). Using microdialysis, we have observed a greater release of norepinephrine (NE) into the interstitia of striated muscle, than that observed in control Wistar-Kyoto (WKY) rats in the prehypertensive phase. We confirmed these results in the subcutaneous adipose tissue where the sympathetic output controls metabolism. This study was carried out in order to evaluate SNS activity in two district tissue types conducted during both the prehypertensive phase (4-5 weeks of age) and the established hypertensive phase (15-16 weeks of age). Interstitial concentrations of NE were measured by microdialysis in striated muscle and subcutaneous adipose tissue. Two groups of rats were studied. Each group was made up of 8 subjects, SHR and WKY, males of 4-5 weeks of age with a mean body weight of 80 and 75 g respectively. Arterial systolic pressure (tail-cuff) values were 106 mmHg (standard deviation +/-8.2) in SHR and 101 mmHg (standard deviation +/-6.9) in WKY rats (NS). Two microdialysis probes were positioned in the subcutaneous fatty tissue and in the striated muscle of the parascapular region and perfused with Ringers' solution. The dialysate was collected every 30 min for 150 min and analyzed in high-performance liquid chromatography-every day. The content of NE and other catecholamines was determined. The same animals in both groups were reevaluated at 15-16 weeks of age. The mean body weight at this time was 246 g for the SHR and 289 g for the WKY rats. Arterial systolic pressure was 161 mmHg (standard deviation +/-13.3) and 108 mmHg (standard deviation +/-15.6) respectively (p < 0.01, Student's t test). Interstitial levels of NE were higher in SHR than in WKY rats in both tissues examined in the prehypertensive phase and in the established hypertensive phase. Mean NE values from subcutaneous adipose tissue in 4-5 week-old SHR were 1362.1 +/- 181.3 pg/ml compared to 479.0 +/- 162.3 pg/ml in WKY rats (p < 0.001, Student's t test). Muscle tissue NE levels in SHR were 1292.7 +/- 319.1 vs 536.3 +/- 146.7 pg/ml in WKY rats (p < 0.001, Student's t test). Values from the same rats at 15-16 weeks of age were 1405.0 +/- 148.3 pg/ml in SHR compared to 501.6 +/- 131.2 pg/ml in fatty tissue from WKY rats and 1893.7 +/- 214.6 vs 502.0 +/- 118.8 pg/ml in muscle tissue from the respective groups (p < 0.001, Student's t test). Significant differences (p < 0.01, Student's t test) were also observed in mean NE values in striated muscle tissue during the developing phase of hypertension. These findings document SNS hyperactivity in SHR when compared to WKY normotensive controls. This increase in SNS activity was observed in both the prehypertensive phase and in the established hypertensive phase indicating a complete disassociation from regional components of regulation (baroreceptor control and metabolic control), at least in the prehypertensive phase. These results may suggest as alteration in primitive sympathetic central outflow. Higher interstitial NE concentrations in the muscle tissue from SHR during the hypertensive phase compared to levels of young animals that are still normotensive, reveal an interesting pathophysiological aspect for the development of arterial hypertension.