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Jaap Deinum

Publications and source records attributed to Jaap Deinum.

23 records · Page 2Linked to original sources
PubMed2002

The Renin-Angiotensin system and vascular disease in diabetes.

Angiotensin II, the effector molecule of the renin-angiotensin system, has profound effects on endothelial and smooth muscle cells. These effects are not only hemodynamic in nature, but also comprise inflammation, thrombosis, and cell proliferation through stimulation of production of cytokines and growth factors. In diabetes mellitus these effects seem amplified with adverse consequences like atherosclerosis and occlusive microangiopathy. Suggestive evidence for this notion is the impressive beneficial effect of pharmacological interference with the renin-angiotensin system in large vessel disease as well as in renal and retinal microangiopathy. Since the circulating renin-angiotensin system does not seem to be activated in diabetes mellitus it is now thought that independent tissue renin-angiotensin systems play a role in diabetic complications. Whether any genetic propensity to diabetic angiopathy resides in genes of the renin-angiotensin system remains to be determined.

Angiotensin II↗
PubMed2002

Optimal dose of losartan for renoprotection in diabetic nephropathy.

BACKGROUND: Angiotensin II subtype-1 receptor antagonists represent a valuable new class of drugs in the treatment of diabetic nephropathy. The aim of our study was to evaluate the optimal dose of losartan for renoprotection and blood pressure reduction in diabetic nephropathy. METHODS: Fifty consecutive hypertensive type 1 diabetic patients with diabetic nephropathy received increasing doses of losartan, 50, 100, and 150 mg once daily in three periods each lasting 2 months. At baseline and at the end of each treatment period, albuminuria, 24-h blood pressure (TM2420 A&D), and glomerular filtration rate (GFR) ([(51)Cr]EDTA plasma clearance) were determined. RESULTS: Baseline values of albuminuria (geometric mean (95% CI)) and GFR (means+/-SEM) were 1138 (904-1432) mg/24 h and 91+/-3 ml/min/1.73 m(2), respectively. The blood pressure at baseline was 155/81+/-3/2 mmHg. All doses of losartan reduced albuminuria and blood pressure. Albuminuria was reduced by 30% (95% CI (15-41)) on losartan 50 mg, 48% (35-57) by losartan 100 mg, and 44% (32-56) by losartan 150 mg (all P values <0.01 vs baseline). Losartan 100 mg daily was significantly more effective than 50 mg daily in reducing albuminuria (P<0.01) without differences between the two high doses. Losartan 50, 100, and 150 mg daily decreased systolic/diastolic blood pressures by 7/4, 12/6, and 10/5 mmHg, respectively (all P<0.05). Losartan 100 mg daily was more effective than 50 mg daily in reducing systolic, diastolic, and mean arterial blood pressure (P=0.05), without differences between the high doses. Treatment with losartan 100 and 150 mg lowered GFR by 4 ml/min/1.73 m(2) (P<0.05). CONCLUSION: Our study suggests that the optimal dose of losartan is 100 mg daily for renoprotection and blood pressure reduction in type 1 diabetic patients with diabetic nephropathy.

Albuminuria↗
PubMed2002

Transendothelial transport of renin-angiotensin system components.

BACKGROUND: Vascular (interstitial) angiotensin (ANG) II production depends on circulating renin-angiotensin system (RAS) components. Mannose 6-phosphate (man-6-P) receptors and angiotensin II type 1 (AT(1)) receptors, via binding and internalization of (pro)renin and ANG II, respectively, could contribute to the transportation of these components across the endothelium. OBJECTIVE: To investigate the mechanism(s) contributing to transendothelial RAS component transport. METHODS: Human umbilical vein endothelial cells were cultured on transwell polycarbonate filters, and incubated with RAS components in the absence or presence of man-6-P, eprosartan or PD123319, to block man-6-P, AT(1) and angiotensin II type 2 (AT(2)) receptors, respectively. RESULTS: Apically applied (pro)renin and angiotensinogen slowly entered the basolateral compartment, in a similar manner as horseradish peroxidase, a molecule of comparable size that reaches the interstitium via diffusion only. Prorenin transport was unaffected by man-6-P. Apical ANG I and ANG II rapidly reached the basolateral fluid independent of AT(1) and AT(2) receptors. Basolateral ANG II during apical ANG I application was as high as apical ANG II, whereas during apical ANG II application it was lower. During basolateral ANG I application, ANG II generation occurred basolaterally only, in an angiotensin-converting enzyme (ACE)-dependent manner. CONCLUSIONS: Circulating (pro)renin, angiotensinogen, ANG I and ANG II enter the interstitium via diffusion, and interstitial ANG II generation is mediated, at least in part, by basolaterally located endothelial ACE.

Angiotensin I↗
PubMed2002

Predictors for clinical success at one year following renal artery stent placement.

PURPOSE: To determine pretreatment variables that may predict 1-year clinical outcome of stent placement for renal artery stenosis. METHODS: In a prospective study, 40 consecutive patients (29 men; mean age 60 +/- 9.1 years) with angiographically proven atherosclerotic renal artery stenosis were treated with stent placement because of drug resistant hypertension (n=14), renal function impairment (n=14), or both (n=12). Clinical success at 1 year was defined as a decrease of diastolic blood pressure > or = 10 mmHg or a decrease in serum creatinine > or = 20%, depending on the indication for treatment. Regression analysis was performed using anatomical parameters from angiography and intravascular ultrasound, estimates of renal blood flow from renal scintigraphy, and single-kidney renal function measurements. RESULTS: Patients treated for hypertension had better outcome than those treated for renal function impairment, with clinical success rates of 85% and 35%, respectively. Preserved renal function, with low serum creatinine and high 2-kidney glomerular filtration rate at baseline, was associated with clinical success in the entire patient group at follow-up (p=0.02 and p=0.03, respectively). An elevated vein-to-artery renin ratio on the affected side was borderline predictive (p=0.06). In patients treated for renal impairment, lateralization to the affected kidney (affected kidney-to-2-kidney count ratio < or = 0.45) on the scintigram emerged as a significant predictor for clinical success, with an odds ratio of 15 (p=0.048). CONCLUSIONS: Clinical success of renal artery stent placement is better for the treatment of hypertension than for preserving renal function. In patients with renal function impairment, lateralization to the affected kidney on the scintigram appears to be a predictor of clinical success.

Aged↗