INDIVIDUAL AND COMBINED EFFECTS OF VERAPAMIL OR TRANDOLAPRIL ON ATTENUATING HYPERTENSIVE GLOMERULOPATHIC CHANGES IN THE STROKE-PRONE RAT

Previous studies have demonstrated differences in the progression to g lomerulosclerosis with the use of calcium channel blockers (CCB). The results with angiotensin-converting enzyme (ACE) inhibitors are more c onsistent. Moreover, only two studies have examined the combined effec ts of these drug classes on the development of glomerulosclerosis, The aim of the study presented here was to test the hypothesis that nonhy potensive doses of the combination (VT) of a nondihydropyridine CCB, v erapamil (V), and an ACE-inhibitor, trandolapril (T), will slow the de velopment of glomerulosclerosis better than either agent alone in stro ke-prone spontaneously hypertensive rats (SHRSP). SHRSP were randomize d to treatment in one of three groups with nonhypotensive doses of the se agents; a fourth group served as control (C). The control rats deve loped significant increases in proteinuria compared with the other gro ups (C, 190 +/- 35 mg . kg(-1). d(-1) versus VT, 19 +/- 12 mg . kg(-1) . d(-1); P < 0.05), This finding correlated with the degree of glomeru losclerosis (mean severity grading for C, 3.31 +/- 0.21 versus VT, 1.6 +/- 0.51; P < 0.05). Moreover, there was no significant reduction in arterial pressure between these groups (C, 282 +/- 5 versus VT, 259 +/ - 13 mm Hg; P = 0.12). Despite persisting hypertension, the rise in pr oteinuria was also attenuated in both the V group (57 +/- 21 mg . kg(- 1). d(-1)) and the T group (43 +/- 24 mg . kg(-1). d(-1)), However, co mpared with the control rats, kidney morphology was unchanged. Lastly, creatinine clearance was better preserved in the VT group compared wi th the control group (C, 0.57 +/- 0.01 versus VT, 0.74 +/- 0.06 ml . m in(-1). 100 g(-1); P < 0.05), It was concluded that the combination of nonhypotensive doses of VT attenuates the rise in proteinuria and pro gression to glomerulosclerosis, This study supports the concept that V T may have effects on the glomerulus that are independent of blood pre ssure reduction.