EFFECTS OF AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, A CALCIUM-ANTAGONIST, AND AN ENDOTHELIN RECEPTOR ANTAGONIST ON RENAL AFFERENT ARTERIOLAR STRUCTURE

Narrowed afferent arteriolar diameter in young, spontaneously hyperten sive rats (SHR) may be a contributor to later development of high bloo d pressure. Thus, treatment that causes dilation of the afferent arter ioles in SHR may inhibit the redevelopment of high blood pressure when treatment is withdrawn. We treated SHR with an ACE inhibitor (cilazap ril, 5 to 10 mg/kg per day, high; 1 mg/kg per day, low), a calcium ant agonist (mibefradil, 20 to 30 mg/kg per day). and an endothelin recept or antagonist (bosentan, 100 mg/kg per day) from age 4 to 20 weeks. Un treated SHR and Wistar-Kyoto rats were also investigated. At 20 weeks, the rats were killed, and morphology of the afferent arterioles was s tudied. Other SHR (untreated, high cilazapril, low cilazapril, mibefra dil) were treated in exactly the same way and then followed to 32 week s without treatment. The morphometric studies showed that cilazapril i ncreased the lumen diameter in the afferent arterioles and decreased t he media-lumen ratio in a dose-dependent manner. On withdrawal of cila zapril treat ment, the reduction in blood pressure persisted. Mibefrad il tended to increase afferent arteriolar diameter, whereas it did not alter media-lumen ratio. The persistent effect on blood pressure was only moderate after withdrawal of mibefradil. Bosentan had no effect o n renal afferent arteriolar structure or blood pressure. In conclusion . cilazapril was more effective than mibefradil in altering afferent a rteriolar structure and caused the most persistent effect on blued pre ssure after treat ment withdrawal. The association of increased affere nt arteriolar diameter and lower blood pressure level after withdrawal of treatment may suggest a pathogenic role fur afferent arteriolar di ameter in the development of high blood pressure in SHR.