ORGAN SPECIFICITY OF ANTIHYPERTENSIVE THERAPY ON OCULAR ALBUMIN VASCULAR CLEARANCE AND ALBUMINURIA IN THE HYPERTENSIVE DIABETIC RAT

Purpose. The contributions of hypertension and diabetes to microvascul ar dysfunction in the kidney and eye were investigated. Two indices of microvascular dysfunction, urinary albumin excretion rate (AER) and a lbumin vascular clearance (AVC) in the eye, were studied in control an d streptozocin diabetic Wistar Kyoto (WKY) and spontaneously hypertens ive rats (SHR). Methods. Studies were performed on four groups of untr eated rats-nondiabetic and diabetic WKY and nondiabetic and diabetic S HR-and on three groups of diabetic SHR treated with a converting enzym e inhibitor (perindopril), a calcium-channel blocker (lacidipine), or triple therapy (hydrochlorothiazide, reserpine, and hydralazine). In a ll rats, AER and AVC were measured at 16 weeks. Results. There was a p rogressive increase in both parameters in the order WKY, diabetic WRY, SHR, and diabetic SHR When compared with nondiabetic WRY, diabetic SH R showed an approximately 30-fold increase in AER and an approximately threefold increase in AVC. Treatment of diabetic SHR with perindopril or triple therapy normalized AER compared to an equihypotensive dose of lacidipine, which had no effect By contrast, the three antihyperten sive regimens showed a different order of efficacy in preventing incre ases in ocular AVC. In diabetic SHR, the increase in retinal AVC was p revented largely by lacidipine, whereas the other two antihypertensive regimens showed lesser effects [AVC expressed as percentage nondiabet ic WKY;. untreated diabetic SHR 278% +/- 47%, lacidipine 93% +/- 10% ( P < 0.001), triple therapy 132% +/- 37% (P < 0.05), and perindopril 16 7% +/- 9% (P < 0.05)]. Lacidipine also prevented the increase in AVC o f the anterior and posterior uvea. By contrast, increases in AVC obser ved in the diabetic SHR were not prevented by perindopril in the poste rior uvea or by triple therapy in the anterior uvea. Thus, hypertensio n and diabetes increased ocular AVC and AER, and effective antihyperte nsive therapy substantially prevented changes in both parameters. Howe ver, despite equivalent levels of blood pressure control for each regi men, discordant effects were noted on AVC and AER Perindopril was asso ciated with significantly lower AER than lacidipine, whereas lacidipin e was more potent in preventing increases in ocular AVC. Conclusions. Results of this study suggest that different antihypertensive regimens in the diabetic rat may exert organ-specific effects on the retina an d kidney despite equivalent effects on systemic blood pressure. These data also raise the possibility that retinal microvascular dysfunction in diabetes is ameliorated more readily by calcium-channel blockade t han by converting-enzyme inhibition, whereas the reverse applies to re nal microvascular dysfunction, as reflected by albuminuria.