Effect of Verapamil and Captopril on Endothelial Injury in the Diabetic Hypertensive Rat

Abstract

Microvascular and macrovascular complications are a major cause of increased morbidity and mortality in patients with diabetes mellitus and hypertension. Atherosclerosis is the major cause of these complications. Recently, Hebden and colleagues demonstrated endothelial injury in a rat model with streptozotocin-induced diabetes mellitus and deoxycorticosterone acetate-induced hypertension. To determine if captopril and verapamil reduce endothelial injury in this model of diabetic hypertensive (DH) rats, we evaluated mean medial thickness and intimal cell changes in four groups of rats: control, untreated DH rats, captopril-treated DH rats, and verapamil-treated DH rats. Mean medial thickness increased from 63.5 +/- 4.8 microns in control rats (n = 7) to 107.2 +/- 7.5 microns in untreated DH rats (n = 8), (P < .05). Verapamil and captopril blunted DH-induced medial thickening to 90.1 +/- 4.9 and 93.7 +/- 8.3 microns, respectively (P < .05 compared with control and untreated rats). An endothelial injury index (EI), consisting of white blood cells adhered to the intimal surface and rounded endothelial cells per 25-microns arc in aortic vessels, was determined for each group. The EI increased from 0.2 +/- 0.1 cells/25-microns arc in control rats to 6.3 +/- 4.0 cells/25-microns arc in untreated DH rats. Both verapamil and captopril diminished the EI in DH rats to 0.8 +/- 0.2 and 2.7 +/- 0.3 cells/25-microns arc, respectively (P < .05 compared with untreated DH rats). In addition, verapamil decreased the EI in DH rats to a greater degree than captopril (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)