Changes in renal hemodynamics in streptozotocin-induced diabetic rats with L-ascorbic acid supplementation.

The present study was designed to investigate whether L-ascorbic acid (AA) supplementation could prevent changes in renal hemodynamics in diabetic rats or not. The experiments were carried out in 48 male Sprague-Dawley rats. Diabetes mellitus was induced in rats by intravenous injection with streptozotocin (STZ) (55 mg/kg.bw), while the control rats were received citrate buffer alone. The renal hemodynamics was examined after the supplementation of AA (1 mg/l) for 8 and 16 weeks. The results demonstrated that AA could retard the increase (p<0.05) in renal vascular resistance (RVR) significantly compared with diabetic rats (STZ). Besides, at week 16, the effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) of STZ-AA were significantly higher than those of STZ (p<0.05). In conclusion, supplementation of AA was able to ameliorate the renal dysfunction in STZ-induced diabetic rats by decrease in RVR concomitant with an increase in both ERPF and GFR.

Effects of a dual inhibitor of angiotensin converting enzyme and neutral endopeptidase, MDL 100,240, on endocrine and renal functions in healthy volunteers.

OBJECTIVE: To investigate the endocrine and renal effects of the dual inhibitor of angiotensin converting enzyme and neutral endopeptidase, MDL 100,240. DESIGN: A randomized, placebo-controlled, crossover study was performed in 12 healthy volunteers. METHODS: MDL 100,240 was administered intravenously over 20 min at single doses of 6.25 and 25 mg in subjects with a sodium intake of 280 (n = 6) or 80 (n = 6) mmol/day. Measurements were taken of supine and standing blood pressure, plasma angiotensin converting enzyme activity, angiotensin II, atrial natriuretic peptide, urinary atrial natriuretic peptide and cyclic GMP excretion, effective renal plasma flow and the glomerular filtration rate as p-aminohippurate and inulin clearances, electrolytes and segmental tubular function by endogenous lithium clearance. RESULTS: Supine systolic blood pressure was consistently decreased by MDL 100,240, particularly after the high dose and during the low-salt intake. Diastolic blood pressure and heart rate did not change. Plasma angiotensin converting enzyme activity decreased rapidly and dose-dependently. In both the high- and the low-salt treatment groups, plasma angiotensin II levels fell and renin activity rose accordingly, while plasma atrial natriuretic peptide levels remained unchanged. In contrast, urinary atrial natriuretic peptide excretion increased dose-dependently under both diets, as did urinary cyclic GMP excretion. Effective renal plasma flow and the glomerular filtration rate did not change. The urinary flow rate increased markedly during the first 2 h following administration of either dose of MDL 100,240 (P < 0.001) and, similarly, sodium excretion tended to increase from 0 to 4 h after the dose (P = 0.07). Potassium excretion remained stable. Proximal and distal fractional sodium reabsorption were not significantly altered by the treatment. Uric acid excretion was increased. The safety and clinical tolerance of MDL 100,240 were good. CONCLUSIONS: The increased fall in blood pressure in normal volunteers together with the preservation of renal hemodynamics and the increased urinary volume, atrial natriuretic peptide and cyclic GMP excretion distinguish MDL 100,240 as a double-enzyme inhibitor from inhibitors of the angiotensin converting enzyme alone. The differences appear to be due, at least in part, to increased renal exposure to atrial natriuretic peptide following neutral endopeptidase blockade.

Divergent effects of calcium channel and angiotensin converting enzyme blockade on glomerulotubular function in cyclosporine-treated renal allograft recipients.

The effects of amlodipine and perindopril on renal hemodynamics and tubular function in cyclosporine-treated hypertensive renal allograft recipients were evaluated in a randomized, double-blind crossover fashion. Ten patients were studied after a 2-week placebo run-in and, after 8 weeks of active treatment, allowing a 2-week placebo washout between treatments. At the end of each period, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured as 51Cr-EDTA and 123I-hippuran clearance, respectively, and tubular function evaluated by the lithium clearance technique was determined. Both drugs maintained GFR and ERPF and lowered mean arterial pressure (MAP, mm Hg) to a similar extent (time x treatment, P = 0.466): amlodipine from 126.9 +/- 2.5 to 115.9 +/- 2.2; perindopril from 126.9 +/- 2.5 to 117.9 +/- 3.9 (time effect of all treatments together, P = 0.003). Accordingly, renal vascular resistance (RVR, mm Hg/mL/min/1.73 m2) was equally reduced (time x treatment, P = 0.955): amlodipine from 0.36 +/- 0.03 to 0.30 +/- 0.02; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01 (time effect all treatments together, P = 0.043). Sodium clearance and fractional excretion of sodium were not affected by either drug. Output of fluid from the proximal tubules measured as clearance of lithium (CLi, mL/min) and uric acid (CUr, mL/min) was higher after amlodipine than after perindopril (CLi 19.1 +/- 2.1 v 16.5 +/- 1.7, P =0.036 and CUr 7.0 +/- 0.6 v 5.9 +/- 0.4, P = 0.007). As a consequence, after amlodipine, distal absolute reabsorption of sodium was higher (DARNa 2.57 +/- 0.28 v 2.19 +/- 0.22 mEq/min, P = 0.027) and serum uric acid was lower (5.9 +/- 0.3 v 6.7 +/- 0.4 mg/dL, P = 0.001) in comparison with perindopril. In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent. Overall sodium excretion is not affected by either agent. Urate clearance is higher and serum uric acid lower on amlodipine as compared with perindopril.

Unchanged renal haemodynamics following high dose ascorbic acid administration in normoalbuminuric IDDM patients.

The object of the study was to test whether high dose ascorbic acid (AA) could normalize glomerular hyperfiltration in insulin-dependent diabetes mellitus (IDDM) patients. A prospective, double-blind, randomized, placebo (tartaric acid, TA) controlled study design was used, with parallel treatment lasting 4 weeks. Measurements were made before and after treatment, on 24 normoalbuminuric, normotensive male IDDM patients, who were randomized to ascorbic acid (n = 12, age 35 years (18-39), diabetes duration 12 years (2-12), BP 128/82 mmHg (SD 14/6)), or to placebo (TA) (n = 12, age 30 years (19-36), diabetes duration 8 years (2-17), BP 119/75 mmHg (SD 9/7). The intervention consisted of 6 enterosoluble tablets of 500 mg AA or 213 mg TA, twice a day, being daily doses of 6 g AA or 2.55 g TA. No significant differences in any of the parameters measured were seen, when comparing results following AA or placebo treatment. The glomerular filtration rate (GFR, clearance of 125I-iothalamate) was unchanged while effective renal plasma flow (ERPF, clearance of 131I-hippuran) tended to decline in both groups. The GFRs before and after treatment in the AA-treated group were 141 (SD 15) and 134 (SD 12) ml min-1 1.73 m-2; NS (2p = 0.09). In the TA-treated group they were 142 (SD 19) and 137 (SD 16) ml min-1 1.73 m-2; NS (2p = 0.20). The ERPFs in the AA group were 584 (SD 93) and 545 (SD 47) ml min-1 1.73 m-2; (2p = 0.06). In the TA group they were 618 (SD 108) and 574 (SD 98) ml min-1 1.73 m-2 (2p = 0.03). The filtration fractions (FFs) in the AA group were 0.244 and 0.246 NS.(ABSTRACT TRUNCATED AT 250 WORDS)