VASOCONSTRICTORS AND RENAL PROTECTION INDUCED BY BETA(1)-SELECTIVE ADRENOCEPTOR ANTAGONIST BISOPROLOL

We investigated the role of the vasoconstrictors endothelin-1 (ET-1) a nd thromboxane in renal protection by the beta(1)-selective adrenocept or antagonist, bisoprolol, in Dahl salt-sensitive rats (Dahl S) and sa lt-resistant rats (Dahl R). Six-week bisoprolol treatment (20 mg/kg ch ow) reduced systolic blood pressure (SBP) by 14% in Dahl S rats fed a high-salt (4% NaCl) diet. This BP reduction was accompanied by a decre ase in aortic wall thickness. ET-1 and thromboxane released from renal cortex was significantly decreased by 17 and 30% with bisoprolol, res pectively. Other prostaglandin synthesis was unaffected. Renal functio n such as proteinuria, N-acetyl-beta-D-glucosaminidase (NAG) excretion , and glomerular filtration rate (GFR) was not influenced by bisoprolo l. Morphologic investigation showed that bisoprolol significantly impr oved glomerular sclerosis by 29% and attenuated arterial damage by 71% , although tubular injury was not affected. The more severe the glomer ulosclerotic lesions, the greater the generation of thromboxane and ET . The arterial lesions were positively correlated to thromboxane gener ation. These data indicate that long-term bisoprolol treatment reduces vasoconstrictive ET-1 and thromboxane generation and that these alter ations may be partly responsible for the amelioration of glomerular an d arterial injury in Dahl S rats.