Effects of an Angiotensin-Converting Enzyme Inhibitor, a Calcium Antagonist, and an Endothelin Receptor Antagonist on Renal Afferent Arteriolar Structure

Abstract

Narrowed afferent arteriolar diameter in young, spontaneously hypertensive rats (SHR) may be a contributor to later development of high blood pressure. Thus, treatment that causes dilation of the afferent arterioles in SHR may inhibit the redevelopment of high blood pressure when treatment is withdrawn. We treated SHR with an ACE inhibitor (cilazapril, 5 to 10 mg/kg per day, high; 1 mg/kg per day, low), a calcium antagonist (mibefradil, 20 to 30 mg/kg per day), and an endothelin receptor antagonist (bosentan, 100 mg/kg per day) from age 4 to 20 weeks. Untreated SHR and Wistar-Kyoto rats were also investigated. At 20 weeks, the rats were killed, and morphology of the afferent arterioles was studied. Other SHR (untreated, high cilazapril, low cilazapril, mibefradil) were treated in exactly the same way and then followed to 32 weeks without treatment. The morphometric studies showed that cilazapril increased the lumen diameter in the afferent arterioles and decreased the media-lumen ratio in a dose-dependent manner. On withdrawal of cilazapril treatment, the reduction in blood pressure persisted. Mibefradil 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 on renal afferent arteriolar structure or blood pressure. In conclusion, cilazapril was more effective than mibefradil in altering afferent arteriolar structure and caused the most persistent effect on blood pressure after treatment withdrawal. The association of increased afferent arteriolar diameter and lower blood pressure level after withdrawal of treatment may suggest a pathogenic role for afferent arteriolar diameter in the development of high blood pressure in SHR.