Immunological dysfunction and enhanced sympathetic activity contribute to the pathogenesis of spontaneous...

Chronic elimination of renal sympathetic nerve activity will prevent one-third of the hypertension in spontaneously hypertensive rats (SHR), and manipulations of the immune system will block one-half of the spontaneous hypertension. In the present study the combined role of enhanced sympathetic activity and immunological dysfunction in the pathogenesis of hypertension in the SHR was investigated. Neonatal SHR received thymic implants from donor Wistar rats. When these thymus-implanted SHR were 6 weeks old they underwent bilateral renal denervation. The renal denervation procedure was repeated when the SHR were 9, 12, 15 and 18 weeks old. When the implanted, denervated SHR were 20 weeks old their average systolic pressure (SP) was 146 +/- 4.0 mmHg (mean +/- s.e.m.). The SP of age-matched, sham-operated Wistar-Kyoto (WKY) rats was 127 +/- 2.2 mmHg, while it averaged 196 +/- 4.4 mmHg in 20-week-old sham-operated SHR. Therefore, neonatal thymic implants in combination with chronic renal denervation abolish three-quarters of the hypertension in the SHR. These results support the hypothesis that immunological dysfunction and enhanced sympathetic activity cause spontaneous hypertension.