POSSIBLE RADICAL SCAVENGING PROPERTIES OF CICLETANINE AND RENAL PROTECTION IN DAHL SALT-SENSITIVE RATS

Much interest in cicletanine, a novel antihypertensive drug, has grown because it uniquely stimulates prostacyclin (PGI2) production and may , thereby, provide further cardiovascular protection. We postulated th at cicletanine may be an antioxidant, and assessed its ability to prot ect the kidney in Dahl salt-sensitive (Dahl S) rats on a high salt die t. Cicletanine eradicated in vitro a stable radical, DPPH, and decreas ed the lipid peroxidation both in rat brain homogenate and in a xanthi ne-xanthine oxidase (X-XOD) superoxide generating system. Furthermore, cicletanine attenuated the inhibition of PGI2 synthase activity by 15 HPETE. However, cicletanine did not exhibit superoxide dismutase-like activity in X-XOD system, suggesting that it behaves primarily as a hy droxy radical scavenger. A 6 week cicletanine treatment reduced blood pressure in Dahl S rats fed a high salt diet, and ameliorated function al and morphological injury to the kidney. This attenuation of glomeru lar sclerosis correlated with the attenuation of lipid peroxidation in the kidney homogenate. These data indicate that cicletanine is an ant ioxidant that protects the kidney from salt-induced hypertension in Da hl salt-sensitive strain rats.