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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 595 records · Page 33Linked to original sources
PubMed1989

Angiotensin formation in the isolated rat hindlimb.

Local vascular generation of angiotensin was investigated in isolated perfused rat hindquarters. Extraction and combined high-performance liquid chromatography (HPLC)/radioimmunoassay analysis of hindlimb perfusate showed a spontaneous release of angiotensin I (Ang I; 5.0 +/- 3.4 fmol/h) and angiotensin II (Ang II; 31.8 +/- 7.9 fmol/h). Angiotensin converting enzyme (ACE) inhibition with captopril abolished Ang II release while Ang I levels increased more than 10-fold. Perfusion with purified hog renin caused a dose-dependent angiotensin release and vasoconstriction. The renin inhibitor H-142 abolished all effects of renin whereas ACE inhibition prevented Ang II formation and vasoconstriction but increased Ang I levels. Metabolism and pressor effects of synthetic tetradecapeptide renin substrate (TDP), Ang I and Ang II were studied using a recirculating rat hindlimb perfusion system. TDP-dependent formation of Ang I and II, and an increase in perfusion pressure was shown; ACE inhibition reduced but did not abolish Ang II formation and vasoconstriction. Ang I was converted to Ang II by about 50% during one pass through a hindlimb. This conversion was abolished by ACE inhibition. These data add support to the presence of a functional vascular renin-angiotensin system.

Angiotensin I↗
PubMed1989

Therapeutic efficacy and tolerance of ramipril in hypertensive patients with renal failure.

In an open trial, the antihypertensive and hormonal effects of ramipril, a new nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, were studied in 23 hypertensive patients with various degrees of renal failure: group I, creatinine clearance 5-15 ml/min, n = 10; group II, creatinine clearance 15-40 ml/min, n = 7; group III, creatinine clearance 40-80 ml/min, n = 6. In a 2-week placebo run-in period, antihypertensive agents were reduced or discontinued. During the treatment phase, patients received a 5-mg tablet of ramipril once daily for a period of 2 weeks. Concomitant medication remained unchanged. In all groups, ramipril significantly decreased mean arterial blood pressure. Blood pressure response was not different in the three groups, although plasma ramipril levels were higher in patients with severe renal failure. In patients with high plasma renin activity (PRA), reduction of blood pressure was greater than in subjects with low PRA. Plasma ACE activity was suppressed to less than 20% of its initial value in all groups during the whole treatment period, and the suppression was more marked and lasted longer in patients with severe renal failure. A strong correlation between the plasma ramiprilat levels and the inhibition of plasma ACE activity was noted for all groups. Mean serum creatinine did not increase significantly; serum potassium levels rose from 4.5 to 4.9 mmol/L on day 14 (p less than 0.01). In conclusion, in patients with various degrees of renal failure, ramipril represents an effective and well-tolerated antihypertensive agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Natriuretic factors and lithium clearance in patients with the syndrome of inappropriate antidiuretic hormone (SIADH)

Because the syndrome of inappropriate antidiuretic hormone (SIADH) is a state of disturbed body fluid volume regulation and altered sodium balance we sought to determine if recently described volume regulatory factors were stimulated in SIADH. We measured atrial natriuretic peptide (ANP), endogenous digitalis-like natriuretic factor (EDNF) and urinary free dopamine in SIADH (n = 27). We also determined fractional clearance of lithium (FCLi). The data obtained in SIADH were compared with similar measurements performed in sodium retaining hyponatremias, such as those of heart failure (n = 26), liver cirrhosis (n = 19) and volume contraction (n = 28). We observed: ANP was 19.5 +/- 2.7 fM/ml in SIADH; it was significantly lower than ANP in cardiac failure, but no different from ANP in volume contraction. Urinary free dopamine was 2.2 +/- 0.8 microM/24 h in SIADH; this was significantly higher than in volume contraction and liver cirrhosis. EDNF (259 +/- 42 nM/24 h) and FCLi (21.4 +/- 2%) were both numerically higher in SIADH than in other hyponatremic disorders; however, the differences did not achieve significance. In conclusion, our observations did not establish a specific role of ANP in chronic stable SIADH. As to the importance of EDNF, dopamine and proximal tubular fluid reabsorption (FCLi) additional work using acute volume changes may demonstrate their participation in the renal sodium handling of SIADH more clearly than our study did.

Aged↗
PubMed1989

Hypertension in chronic idiopathic glomerulonephritis: analysis of 311 biopsied patients.

Prevalence of hypertension and relation of hypertension to renal function, type of glomerulonephritis or histological features were evaluated in 311 patients with idiopathic chronic glomerulonephritis. The overall prevalence of hypertension was 49.8%. At least in women, prevalence of hypertension was increased even at serum creatinine levels less than 1.1 mg dl-1 compared with the local general population. Prevalence of hypertension was 2.12 and 8.6 fold higher at serum creatinine 1.1-1.4 mg dl-1 in males and females respectively. In patients with untreated hypertension, a relation was found between mean blood pressure and subsequent decline of estimated GFR. Furthermore, in patients with arterial sclerosis, but not in patients without, a significant relation was found between blood pressure and subsequent increase in serum creatinine.

Adolescent↗
PubMed1989

Mobilizable lead in patients with chronic renal failure.

Blood lead (Pb) and urinary Pb before and after i.v. infusion of 1 g of Na2Ca EDTA were determined (atomic absorption) in 46 control subjects and 91 patients with various stages of renal failure (median serum creatinine 2.5 mg dl-1). Under baseline conditions, patients with renal failure had higher blood Pb levels (112 ng ml-1, range 44-272 vs. 76; 36-187 in controls; P less than 0.001) and lower urinary Pb (16.2 nmol 24 h-1 1.73 m-2, 4.86-66.8 vs. 33; 11-91 in controls; P = 0.001). The increment in urinary Pb after EDTA infusion (mobilizable Pb) was higher (795 nmol 4 days-1 1.73 m-2, range 155-5611 vs. 307; 131-1587 in controls; P = 0.001). In 12 patients with renal failure (13%) mobilizable Pb was above the highest value in controls. Mobilizable urinary Pb correlated (r = 0.68) significantly (P = 0.001) with blood Pb, but only marginally with serum creatinine (r = 0.32; P less than 0.007). Mobilizable Pb was higher in patients with renal failure and a history of smoking or occupational Pb exposure and tended to be higher in patients with alcoholism. Ten of 91 patients had gout; increased mobilizable Pb was present in three of the 10. The data confirm relatively high prevalence of elevated body Pb burden in European patients with chronic renal failure. The question is unresolved whether Pb plays a role in the progression of renal failure.

Adolescent↗
PubMed1989

Hyperparathyroidism and abnormal calcitriol metabolism in the spontaneously hypertensive rat.

Abnormalities of calcium metabolism and of its two principal regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol), have been reported in the spontaneously hypertensive rat (SHR). Reports of abnormal calcitriol metabolism in the SHR by several groups have not provided measurements of tissue calcitriol receptors. Similarly, few data are available as to the parathyroid status of the SHR. In the present study, circulating calcitriol levels and intestinal and parathyroid gland calcitriol receptor status were determined in male SHR and in Wistar-Kyoto (WKY) rats. Parathyroid status was investigated by determination of parathyroid gland mass together with tissue micromorphometry and by quantitative histology of bone as a measure of the biological action of parathyroid hormone. Circulating calcitriol levels were reduced in the 11-week-old SHR compared with the WKY rat (165 +/- 23 vs. 194 +/- 28 pmol/l, p less than 0.01, mean +/- SD). Calcitriol-free ratio was diminished and maximal specific binding capacity for calcitriol was increased in the SHR in parathyroid tissue (172 +/- 4.9 vs. 123 +/- 6.6 fmol/mg protein, p less than 0.01) and in intestinal mucosa with no change of receptor affinity. Plasma ionized calcium (1.29 +/- 0.05 vs. 1.45 +/- 0.35 mmol/l, p less than 0.05) and phosphate (1.5 +/- 0.26 vs. 2.4 +/- 0.03 mmol/l, p less than 0.05) were significantly lower in the SHR. Parathyroid gland mass was increased in the SHR (59 +/- 12 vs. 17 +/- 7 micrograms/100 g body wt, p less than 0.001) as a result of hyperplasia and not hypertrophy. Higher osteoclast numbers were observed in SHR bone (27.6 +/- 0.79 vs. 23.9 +/- 0.66 osteoclasts/mm2, p less than 0.01), suggesting increased parathyroid hormone activity. In summary, in the 11-week-old SHR we observed reduced circulating calcitriol levels together with increased tissue calcitriol receptor numbers, increased parathyroid gland mass, and histological evidence of hyperparathyroidism. It is possible that these abnormalities influence the development of hypertension in the SHR.

Animals↗
PubMed1989

Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries.

Because 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to play roles in both proliferation and differentiation of novel target cells, the potential expression of 1,25(OH)2D3 receptor (VDR) activity was investigated in cultured bovine aortic endothelial cells (BAEC). Receptor binding assays performed on nuclear extracts of BAEC revealed a single class of specific, high-affinity VDR that displayed a 4.5-fold increase in maximal ligand binding (Nmax) in rapidly proliferating BAEC compared with confluent, density-arrested cells. When confluent BAEC were incubated with activators of protein kinase C (PKC), Nmax increased 2.5-fold within 6-24 h and this upregulation was prevented by sphingosine, an inhibitor of PKC, as well as by actinomycin D or cycloheximide. Immunohistochemical visualization using a specific MAb disclosed nuclear localized VDR in venular and capillary endothelial cells of human skin biopsies, documenting the expression of VDR, in vivo, and validating the BAEC model. Finally, additional experiments indicated that BAEC formed the 1,25(OH)2D3 hormonal metabolite from 25(OH)D3 substrate, in vitro, and growth curves of BAEC maintained in the presence of 10(-8) M 1,25(OH)2D3 showed a 36% decrease in saturation density. These data provide evidence for the presence of a vitamin D microendocrine system in endothelial cells, consisting of the VDR and a 1 alpha-hydroxylase enzyme capable of producing 1,25(OH)2D3. That both components of this system are coordinately regulated, and that BAEC respond to the 1,25(OH)2D3 hormone by modulating growth kinetics, suggests the existence of a vitamin D autocrine loop in endothelium that may play a role in the development and/or functions of this pathophysiologically significant cell population.

Animals↗
PubMed1989

Immunohistochemical detection of 1,25-dihydroxyvitamin D3 receptors and estrogen receptors by monoclonal antibodies: comparison of four immunoperoxidase methods.

We developed an immunohistochemical method for visualization of vitamin D (VDR) and estrogen receptors (ER) in cryostat sections, using monoclonal antibodies (MAb) to the vitamin D receptor and estrogen receptor, respectively. This method is based on an avidin-biotin labeling technique (LAB). To establish a reliable and sensitive method which can be used easily as a routine diagnostic procedure, we systematically compared four different immunoenzymatic methods with respect to their efficiency in detecting vitamin D and estrogen receptors. Compared to the indirect bridged avidin-biotin (IBRAB), the peroxidase- anti-peroxidase (PAP), and the avidin-biotin complex (ABC) methods, the LAB method produced stronger staining intensities and had higher detection efficiency for both vitamin D and estrogen receptors. In addition, the LAB method had a higher spatial resolution compared to the ABC technique in detection of VDR in normal human skin biopsies. In the case of steroid receptors, i.e., nuclear antigens, immunohistochemistry must deal with a relatively low number of antigenic sites per cell, restricted accessibility of the antigens, and slight differences in antigen concentrations among cells. Under these particular conditions, the chemical properties of the conjugates used in the LAB method may explain why it is superior to the other methods. Consequently, the LAB method is recommended for visualization of ER and VDR.

Animals↗
PubMed1989

Influence of parathyroidectomy on blood pressure and vascular reactivity in spontaneously hypertensive rats.

We investigated the influence of parathyroidectomy (PTX) on blood pressure (BP) and hindlimb vascular reactivity to noradrenaline (NA) and vasopressin (AVP) in male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKR). Three groups of SHR and WKR, respectively, were investigated: Sham-operated (SO) rats on a normal calcium intake (0.95%), SO rats on moderately elevated calcium intake (1.6% calcium diet) and PTX rats on the 1.6% calcium diet. At the end of the experiment (3 months), directly or indirectly measured BP was significantly lower in the PTX-SHR group on the 1.6% calcium diet than in SO-SHR on the same diet. In WKR groups, no changes of BP were recorded. Hindlimb perfusion with oxygenated Tyrode's solution for cumulative dose response curves with NA (0.1-1000 x 10(-6) M) and AVP (0.5-500 x 10(-9) M) showed no differences between PTX and SO groups. Maximal pressures and ED50 for agents used were significantly higher in SHR than WKR groups (p less than 0.05). The results support the hypothesis that the parathyroid glands contribute to high blood pressure in SHR. However, the antihypertensive action of PTX was not mediated by a change in hindlimb vascular reactivity.

Animals↗
PubMed1989

[Immunogenetics of mesangial IgA glomerulonephritis and Schönlein- Henoch purpura].

We have recently examined polymorphisms of immunoglobuline heavy chain genes at S mu and S alpha 1 switch region loci by RFLP technique and described differences of genotype frequencies between healthy controls and patients with IgA-nephritis and Henoch-Schönlein-Purpura respectively. In the present study we further characterized the heavy chain constant region of IgG2 and IgG3 and, in addition, a hypervariable region (D 14 S 1) of unknown function localized downstream. In the present larger patient cohort we confirmed a higher frequency of S alpha 1 7.4 kb homozygotes in patients with IgA-nephritis (but not SHP), i.e. 62.0% vs 38.8% in controls, p less than 0.001. Compared to controls RFLP-frequencies of the constant region of IgG2 were also different in patients with IgA-nephritis, but not RFLP frequencies of D 14 S 1 or of the constant region of IgG3. Patients with IgA-nephritis homozygote for 7.4 kb in S alpha 1 had more adverse renal outcome and hypertension and more severe histological lesions (i.e. interstitial fibrosis, p less than 0.005).

Gene Frequency↗
PubMed1989

[Acquired cystic kidney disease and autosomal dominant polycystic kidney disease--precancerous condition?].

Acquired cystic kidney disease (ACKD) is a frequent complication of end-stage renal disease. In about 50% of patients on chronic haemodialysis treatment, secondary cysts are detected by sonography/computed tomography or at autopsy. ACKD is associated with an increased risk for the development of renal neoplasias. Renal adenomas are found in 8.8% of the cases, renal cell carcinomas are observed in 2.9% of the patients. The prevalence of renal cell carcinoma is 5-10 times greater in ACKD than in the general population. Therefore, ACKD should be considered as a precancerous condition carrying an increased risk for the development of renal cell carcinoma. Consequently patients with ACKD need careful and regular clinical observation and monitoring by ultrasound or computed tomography. An increased risk for the development of renal cell carcinoma has also been discussed in autosomal dominant polycystic kidney disease (ADPKD) based on anecdotal observations. A careful analysis of the literature as well as a retrospective examination of 86 necropsies (1951-1985) and 25 nephrectomy specimens with ADPKD revealed only one patient with renal cell carcinoma. With respect to the incidence of renal cell carcinoma and the frequency of ADPKD (1:1000) in the general population, the present data do not permit the conclusion that ADPKD represents a precancerous condition.

Genes, Dominant↗
PubMed1989

Reaction patterns of the myocardial interstitium in different models of cardiac hypertrophy--stereological investigations.

Several experimental models of cardiac hypertrophy were investigated in rats: 1. mild hypertrophy induced by physical exercise (18 weeks), 2. mild hypertrophy induced by renovascular hypertension (24 weeks), 3. moderate hypertrophy induced by renovascular hypertension in diabetic and non-diabetic animals (8 weeks), 4. moderate hypertrophy induced by renovascular hypertension in diabetic and non-diabetic animals (12 weeks), 5. moderate hypertrophy induced by thyroxin application (4 weeks), 6. mild hypertrophy in chronic uremia (5/6 nephrectomy, 3 weeks). It is concluded from quantitative stereological parameters of the left ventricular papillary muscles that 1. in hypertrophic hearts myocardial blood flow and oxygen consumption, respectively, rather than the size of muscle fibres determine the capillary supply of the myocardium, 2. interstitial fibrosis occurs in hypertrophy induced by chronic pressure overload and depends on degree and duration of hypertension, 3. the extent of interstitial fibrosis in hypertension is magnified by diabetes mellitus, and 4. the interstitial fibrosis which occurs in chronic uremia is not caused by hypertension.

Animals↗