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ABSTRACT Objective The aim of this study was to assess the relationship between retinal vascular caliber and target organ damage in HT patients. Methods Data were collected on cardiac, renal, vascular, and retinal variables in 88 consecutive never-treated HT subjects. Retinal vascular calibers were measured from fundus photographs by using a semi-automated computer-assisted program and summarized as CRAE and CRVE. Results Mean CRAE and CRVE were significantly lower in patients with left ventricular hypertrophy (left ventricular mass ≥110 g/m² for women, 125 g/m² for men) than in those with normal left ventricular ( CRAE: 129.4±3.7 vs 138.2±2.3 μm; P=.04; CRVE: 195.6±4.4 vs 209.8±2.7 μm; P=.008). CRAE and CRVE were negatively correlated with urinary albumin excretion (β± SE=−15.4±3.2, P<.0001 and β± SE=−11.9±4.4, P=.001, respectively) but were not correlated with estimated glomerular filtration rate ( P=.21 and P=.75, respectively), carotid-to-femoral pulse wave velocity ( P=.24 and P=.14), or carotid augmentation index ( P=.43 and P=.16). Conclusion In never-treated HT patients, reduced CRAE and CRVE were associated with cardiac and renal preclinical damage, ie, left ventricular hypertrophy and albuminuria, but not estimated glomerular filtration rate or vascular stiffness. [ABSTRACT FROM AUTHOR]

. Purpose: To assess the relation between retinal vascular caliber and renal function. Patients and methods: Eighty apparently healthy subjects screened for cardiovascular risk factors (mean age 47 years, 51% female, 36% hypertensive, without diabetes or renal dysfunction) were recruited. Retinal vascular calibers were measured from fundus photographs and expressed as central retinal artery and venular equivalent. Renal function was assessed by measurement of glomerular filtration rate (urinary clearance of 99mTc-DTPA) and urinary albumin/creatinine ratio. Results: Mean glomerular filtration rate was 117 ml/min/1.73m2. Overall, central retinal artery and venular equivalent were positively correlated with glomerular filtration rate ( r = +0.31, p = 0.005 and r = +0.30, p = 0.006, respectively). In addition, central retinal artery equivalent was negatively correlated with urinary albumin/creatinine ratio ( r = −0.34, p = 0.002). No significant relationship was found between central retinal venular equivalent and urinary albumin/creatinine ratio ( r = +0.12, p = 0.32). The observed relations between retinal vascular calibers and renal function parameters remained significant after adjusting for potential confounding factors. Conclusion: In apparently healthy subjects with normal renal function, retinal arteriolar and venular calibers were negatively correlated with kidney function, suggesting common determinants of these preclinical target organ damages. [ABSTRACT FROM AUTHOR]

1. Time course of renal alterations associated with long-term (since weaning) administration of a high sodium (HS, 8% NaCl) diet was assessed in Sprague-Dawley rats. Reversal by acute administration of the mineralocorticoid receptor antagonist, potassium canrenoate (40 mg/kg, i.p.) or the type 1 angiotensin II receptor antagonist, losartan (10 mg/kg, i.v.), was evaluated at the age of 5 months (i.e. after 21 weeks of HS feeding). 2. High sodium intake had no detectable effect on blood pressure; however, albuminuria was always higher in the HS than control group. Glomerular filtration rate, renal plasma flow and filtration fraction decreased significantly after 12 weeks of HS diet by approximately 50, 30 and 20%, respectively. Canrenoate was effective and markedly reversed the renal hypofiltration associated with HS feeding without change in systemic blood pressure. In contrast, losartan reduced blood pressure and it was devoid of a beneficial effect on renal function. 3. The present observations indicate that hypofiltration and hypoperfusion of the kidney occurred progressively and require a long period of exposure to a high sodium intake. Albuminuria, which increased before detectable changes in renal function, may represent an early marker of renal dysfunction. The beneficial effect of acute administration of potassium canrenoate favours the participation of aldosterone, at least partially, in the sustained deterioration of renal function after 21 weeks of high sodium feeding. [ABSTRACT FROM AUTHOR]

SUMMARY 1. The participation of endothelin (ET) in the development and maintenance of hypertension induced by angiotensin (Ang) II was assessed using the non-specific ET receptor antagonist bosentan (30 mg/kg per day). 2. In the prevention study, bosentan was given 24 h prior to and during the 17 day period of AngII infusion (200 ng/kg per min, s.c., osmotic pump), whereas in the treatment study, bosentan was administered from day 10 to day 17. Tail-cuff pressure (TCP) was measured before and on days 10 and 17 of AngII infusion. At the end of studies, heart weight index was calculated as the ratio of heart to bodyweight (HWI) and the wall thickness of the carotid artery (perfusion/fixation at 120 mmHg) was measured. Tail-cuff pressure increased from 129 ± 3 to 179 ± 7 and 189 ± 9 mmHg on days 10 and 17 of AngII infusion, respectively. 3. Final TCP was markedly lowered in rats pretreated with bosentan, whereas TCP remained comparable with untreated hypertensive rats when bosentan was given from day 10 of AngII infusion (177 ± 9 mmHg). 4. The increase in cardiac mass associated with AngII hypertension was similarly attenuated in the two groups receiving bosentan. 5. The HWI was 3.49 ± 0.12 mg/g in untreated hypertensive rats and 3.18 ± 0.08 and 3.11 ± 0.09 mg/g in rats pretreated with bosentan and those receiving the antagonist from day 10. 6. The increase in carotid wall thickness induced by AngII was prevented, but not reversed, by bosentan. 7. These results support the hypothesis that endogenous ET participates only in the initial phase of AngII hypertension. In addition, the beneficial effect of bosentan of cardiac mass but not on arterial wall thickness is in favour of a role of ET as a local mediator of the cardiac hypertrophic effect of AngII, independently of the level of blood pressure and duration of hypertension. [ABSTRACT FROM AUTHOR]

For people with chronic renal insufficiency, the therapeutic goal is to prevent progression to end-stage renal disease, a serious condition that can only be treated with dialysis and kidney transplantation. Although restriction of dietary protein slows the progression of renal disease somewhat, the principal treatment to slow chronic renal disease is appropriate reduction of blood pressure. Antihypertensive agents, particularly those that produce sustained, long-term reductions in proteinuria, such as angiotensin-converting enzyme inhibitors, not only decrease blood pressure but also preserve renal function. Clinical trials to evaluate these and other drug therapies in renal disease progression have used both “hard end points” (e.g., dialysis, transplantation, death) and intermediate end points of renal disease progression (e.g., doubling of serum creatinine concentration, reductions in proteinuria). Trials that have used hard end points typically recruited patients with advanced renal disease to demonstrate a difference in therapies within a period of 2 to 5 years. However, proteinuria reduction, along with a decrease in the time to doubling of serum creatinine in very early diabetic renal dis-ease, could demonstrate an altered natural history of renal disease. Although hard end points are indicators of a drug's efficacy in reducing cardiovascular events or preserving renal function, they do not assess the impact of a treatment on altering the natural history of early renal disease. For clinical trials of people with all but the most advanced renal disease, use of intermediate end points of renal disease progression is the only practical option for assessment of treatment efficacy and effectiveness. Given the available data on proteinuria reduction and doubling of serum creatinine from clinical trials, these end points, taken together, appear to provide an acceptable means of assessing a treatment's impact on slowing renal disease progression. [ABSTRACT FROM PUBLISHER]