ROLE OF BETA-ADRENOCEPTOR ON RENAL INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR IN SPONTANEOUSLY HYPERTENSIVE RATS

We have shown previously in the spontaneously hypertensive rat (SHR) k idney that interleukin-6 (IL-6) and tumor necrosis factor (TNF) mRNA l evels were low under conditions of acute anaesthesia and surgical stre ss. The reasons for the suppression of IL-6 and TNF gene expression in the SHR were investigated by examining the influence of enhanced beta -adrenergic stimulation, high blood pressure, and renal function (rena l blood flow,glomerular filtration rate, plasma creatinine levels) on renal IL-6 and TNF mRNAs. The experiments were performed by means of t he following three studies; (1) SHR and Wistar rats at 4, 7, 9 week ol d were injected with lipopolysaccaride (LPS), and then a relationship between blood pressure levels and IL-6 and TNF mRNA levels were estima ted, (2) isoproterenol and propranolol were administered into SHR and WKY rats, and the levels of IL-6 and TNF mRNA were compared, (3) under condition of anaesthesia and surgical stress, blood pressure and rena l functions in SHR were measured, and then the relationships between t hese factors and IL-6 or TNF mRNA levels were analyzed. Renal IL-6 and TNF mRNAs in SHR remained low even though blood pressure increased wi th age and there was no significant correlation between IL-6 or TNF mR NA levels and values of blood pressure or renal function under anaesth esia and surgical stress. However, the inhibition of the IL-6 and TNF mRNAs in SHR was prevented by propranolol treatment. These results sug gested that suppression of IL-6 and TNF mRNAs in the SHR kidney could be due to overactivity of beta-adrenergic influences which may importa ntly contribute to the development of hypertension.