Tomas Lenz

Contribution of angiotensin i converting enzyme gene polymorphism and angiotensinogen gene polymorphism to blood pressure regulation in essential hypertension

The renin-angiotensin system (RAS) is involved in the pathogenesis of essential hypertension. In the present study we examined the genotype frequencies of the insertion/deletion polymorphisms of the ACE gene and the M235T polymorphism of the Angiotensinogen (Agt) gene in patients with essential hypertension in comparison with normotensive subjects. In hypertensive patients functional effects of blood pressure response to ACE inhibition were investigated. A total of 121 patients with essential hypertension (group 1) and 125 normotensive control subjects (group 2) were included in this study. All patients were genotyped by polymerase chain reactions (PCR) for the insertion/deletion (I/D) polymorphism of the ACE gene and the M235T polymorphism of the Agt gene. To analyze possible functional impacts on blood pressure regulation 50 mg of captopril was administered to hypertensive patients. No significant association of essential hypertension with polymorphisms of the Agt and ACE gene was found. The ACE serum levels in patients with the DD-genotype of the ACE I/D polymorphism were higher than in patients with the II-genotype (P < .01). In patients with the ID-genotype the ACE serum levels were in-between. A captopril test was performed in hypertensive patients. The patients were further divided into subgroups according to the diastolic and systolic blood pressure response. Group 1a consisted of patients with a diastolic blood pressure drop of > 5 mm Hg and group 1b with < or =5 mm Hg. Group 1c consisted of patients with a systolic blood pressure drop of > 10 mm Hg and group 1d with < or =10 mm Hg. Twice as many patients with the DD genotype of the ACE gene were found in group 1a compared to group 1b (chi(2) = 5.673; P = .017). No association of systolic blood pressure change to the investigated polymorphisms was found. Our results do not support the hypothesis that the investigated polymorphisms contribute to essential hypertension. Furthermore, no major impact of these polymorphisms on blood pressure response to captopril were detected. We conclude that the investigated genotypes have no influence on blood pressure level and homeostasis.

Vascular Endothelial Growth Factor in Diabetic Nephropathy

Background: Vascular endothelial growth factor (VEGF) increases endothelial permeability. VEGF is produced in podocytes and functional receptors are located on endothelial glomerular cells. The aim of the current study in diabetic patients with normal renal function to various degrees of proteinuric nephropathy was therefore to unravel a possible role of the most important isoform VEGF165 for albuminuria and to investigate the impact of therapy with an inhibitor of the renin-angiotensin system on VEGF165 secretion. Subjects and Methods: A cross-sectional study in 72 patients (41 female, 31 male) with long-standing type 1 (n = 35, mean age 43.3 years, range 22–67) or type 2 (n = 37, mean age 66 years, range 53–83) diabetes mellitus was performed; in 19 patients the serum creatinine value was >1.5 mg/dl. Twenty-six healthy volunteers (17 female, 9 male, mean age 34.8 years, range 19–58) with normal renal function served as controls. Serum and urinary VEGF165 was measured by ELISA. Urinary albumin was measured nephelometrically. Mann Whitney U tests were used for comparisons. Results: In type 1 and type 2 diabetics mean urinary VEGF165 concentration amounted to 112 ± 88 (mean ± SD) and 88 ± 85 ng/l, respectively, compared to 101 ± 60 ng/l in the normal volunteers (NS vs. diabetics). The respective mean urinary albumin concentrations were 443 ± 1029, 394 ± 749 and 20 ± 33 mg/l (p < 0.01 vs. diabetics type 2). There was a correlation between urinary VEGF and albumin, but only in patients with type 2 diabetes (R = 0.497; n = 36; p = 0.002). Urinary VEGF165 was similar in patients with (n = 40) and without ACE inhibitor/AT1 antagonist therapy (n = 32) and in normal volunteers, whereas serum VEGF165 was higher in the treated type 1 diabetics. Conclusions: These results may suggest that VEGF165 plays some role in the development of albuminuria in diabetic nephropathy due to type 2 but not type 1 diabetes.

Immunosuppressive therapy regimen and platelet activation in renal transplant patients

Increased platelet activation caused by an immunosuppressive therapy regimen may contribute to the high incidence of death from cardiovascular disease in renal transplant patients. Cyclosporine (INN, ciclosporin) and azathioprine are reported to activate platelets, but data are rare and controversial for tacrolimus and mycophenolate mofetil.

Effect of angiotensin II infusion with and without angiotensin II type 1 receptor blockade on nitric oxide metabolism and endothelin in human beings: a placebo-controlled study in healthy volunteers.

Angiotensin II has been shown to induce the synthesis of endothelium‐derived relaxing factor nitric oxide (NO) and endothelin in vitro. In human beings, to our knowledge, no data on NO release in response to angiotensin II and on the influence of angiotensin II type 1 receptor blockade have been published.

Prorenin and active renin in human fetal circulation

Pregnancy is associated with high circulating renin and prorenin levels in the maternal (1, 2) and fetal circulation ( 3 ) . Besides secretion from the kidneys, prorenin and renin release by extrarenal tissues, e.g. from reproductive organs, may contribute to the elevated plasma levels during gestation. The majority of renin in reproductive organs is in the form of prorenin, the biosynthetic precursor of renin (4). High concentrations of prorenin are present in placenta, uterus, decidua, ovarian follicular and amniotic fluid of humans, rabbits and nephrectomized dogs (5 ) . In the placenta the site of the highest prorenin concentrations is the peripheral fetal membranes, whereas the levels in the discoid placenta with juxtaposition to the maternal circulation are about 20-fold lower (4). Angiotensinogen, the substrate for the enzyme renin, is also present in placental tissue. Recently, it was demonstrated that the majority of placental angiotensinogen is a high molecular weight form (6), which also can be found in plasma of pregnant women (7). Interestingly, this high molecular weight angiotensinogen predominates in placental regions where the renin levels are high (6). The purpose of the current study was to investigate whether prorenin, renin and renin substrate are released from the uteroplacental unit into the fetal circulation. Patients and methods

Release of prorenin and placental hormones from superfused minced chorion laeve

Subject. Prorenin, the biosynthetic precursor of renin, is present in organs of the human reproductive system.