Antihypertensive therapy must control glomerular hypertension to limit glomerular injury

Male Munich-Wistar rats were subjected to 1-2/3 nephrectomy. One group received no therapy. A second group received the angiotensin converting enzyme (ACE) inhibitor enalapril. A third group received triple therapy (TRX) with reserpine, hydralazine and hydrochlorothiazide. Half of the rats underwent micropuncture study 4 weeks after nephrectomy. Untreated rats exhibited high systemic blood pressure (SBP) and single-nephron hyperfiltration due to high values for the mean glomerular capillary hydraulic pressure (P̄(GC)) and glomerular capillary plasma flow rate (Q(A)). The ACE inhibitor therapy controlled both SBP and P̄(GC). In contrast, TRX normalized SBP but failed to lower P̄(GC). After 12 weeks untreated rats demonstrated systemic hypertension, progressive proteinuria and extensive glomerular sclerosis. The ACE inhibitor dramatically limited proteinuria and sclerosis. Despite equivalent SBP control with TRX, failure to control P̄(GC) resulted in proteinuria and sclerosis comparable with the untreated rats. Thus, unless P̄(GC) is controlled, SBP control may be insufficient to prevent renal injury.