Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptozotocin (STZ)-diabetes was induced in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats with their litter mates serving as controls. The animals were studied for 6 months and blood pressure, weight, urinary and serum glucose, creatinine clearance, total proteinuria and albuminuria were measured monthly. With induction of diabetes, there was a significant rise in creatinine clearance in the hypertensive diabetic animals (SHR-STZ). SHR-STZ (n = 6) developed higher levels of total proteinuria than WKY-STZ (n = 5) although the rise from basal levels was only apparent after 20 weeks of diabetes. All SHR-STZ developed albustix positive proteinuria after 6 months of diabetes. In the first 12 weeks after onset of diabetes, albuminuria increased to a greater degree in SHR-STZ than in WKY-STZ. This occurred before there was a detectable rise in total proteinuria. The SHR-STZ model of genetic hypertension and diabetes may be suitable for the evaluation of antihypertensive therapy in human diabetic renal disease.
 ...
PMID:Accelerated progression of diabetic nephropathy in the spontaneously hypertensive streptozotocin diabetic rat. 380 81

Angiotensin II (Ang II) is the primary mediator of the renin-angiotensin system (RAS). Inappropriate control of the RAS is critically involved in the development and maintenance of hypertension and congestive heart failure. The actions of Ang II are thought to be mediated by specific surface receptors on the various target organs. At present, two receptors for Ang II have been firmly established in mammals, including man. According to current nomenclature, losartan represents the prototype antagonist of the Ang II type 1 (AT1) receptor and does not possess significant affinity for the so-called AT2 receptor. Losartan is the first of a new class of orally active, nonpeptide Ang II receptor antagonists able to very specifically and selectively inhibit the RAS while lacking the agonistic effects of the peptide receptor antagonists, e.g. sarlasin, or the bradykinin potentiating effects of the angiotensin converting enzyme (ACE) inhibitors. Virtually all of the known actions of Ang II, e.g. those defined by Ang II itself, saralasin, ACE or renin-inhibitors are blocked by losartan, emphasizing the major role of this distinct Ang II receptor subtype in mediating the responses of Ang II. The functional correlate of the AT2 receptor remains poorly understood. In several models of experimental and genetic hypertension, AT1 receptor antagonists are effective antihypertensive agents with similar efficacy to that of ACE and renin-inhibitors. In animal models of renal disease, AT1 receptor antagonists significantly decrease proteinuria, protect against diabetic glomerulopathy and increase survival in stroke-prone spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A new class of therapeutic agents: the angiotensin II receptor antagonists. 763 3

Several animal models of genetic hypertension have been developed but not all of them possess a closely related control strain. Therefore, a new model based on Wistar rats is described in which both hypertensive and normotensive lines were bred from a single parental pair. Several basic data on the two lines (called the Prague Hypertensive Rat, PHR, and the Prague Normotensive Rat, PNR) are given. PNR had a longer survival compared with PHR. At the age of 7 weeks, systolic blood pressure was 161 +/- 14 mmHg in PHR males and 109 +/- 9 mmHg in PNR males. Its further increase with age was very slow in PNR but very steep in PHR. Typical left ventricular cardiac hypertrophy developed in PHR in which cardiac output was not significantly different from that of PNR but total peripheral resistance was higher. Kidney weight was also greater in PHR than in PNR. There was no difference in basic renal functions except of proteinuria which was higher in PHR than in PNR. No differences were observed in extracellular and interstitial fluid volumes whereas plasma and blood volumes were slightly but significantly greater in PHR than in PNR suggesting a shift of extracellular fluid towards the intravascular compartment. This hypertensive model the parameters of which resemble to those of human essential hypertension should be especially suitable for cross-transplantation studies.
 ...
PMID:The Prague Hypertensive Rat: a new model of genetic hypertension. 840 16

It has been suggested that hereditary risk for hypertension and cardiovascular disease (CVD) as well as intrauterine growth may be involved in the pathogenesis of diabetic nephropathy. In the present study, we investigated the influence of familial and perinatal risk factors on the occurrence of micro- and macroalbuminuria in young IDDM patients. A cohort of 1,150 young patients with > or =5 years' duration of IDDM was screened for microalbuminuria. Data on family history of hypertension, CVD, IDDM, and NIDDM; perinatal factors such as birth weight, gestational age, and duration of breastfeeding; and maternal education, smoking, hypertension, and proteinuria during pregnancy were collected. We identified 75 patients with an albumin excretion rate > or =15 microg/min in more than two overnight urinary samples and compared them in a nested case-control study with three normoalbuminuric control subjects per patient from the same cohort, matched for diabetes duration. Perinatal factors were analyzed in all patients born at term (+/- 2 weeks), 59 of the 75 patients and 155 of the 225 control subjects. In univariate analysis, hypertension in parents (odds ratio [OR] 4.21), CVD in parents and grandparents (OR 1.26), maternal smoking during pregnancy (OR 3.21), and a low level of maternal education (OR 2.33) were significantly associated with the development of micro- and macroalbuminuria. When adjusted for other familial and perinatal factors, current mean blood pressure, HbA1c, smoking, BMI, sex, age, and postpubertal diabetes duration, using logistic regression analyses, only parental hypertension in all patients and maternal smoking during pregnancy and low level of maternal education in full-term patients were independent risk factors. When patients with poor glycemic control were analyzed separately, familial CVD, poor metabolic control, parental hypertension, maternal smoking during pregnancy, and level of maternal education were independent risk factors, with the adjusted OR markedly increased, compared with the matched subgroup with better HbA1c. In conclusion, familial hypertension and CVD, maternal smoking during pregnancy, and low level of maternal education may independently increase the risk for incipient nephropathy in full-term offspring who later develop IDDM. Current poor glycemic control seemed to increase the effect of these risk factors.
 ...
PMID:Familial and perinatal risk factors for micro- and macroalbuminuria in young IDDM patients. 964 37

In the Prague hypertensive rat (PHR), a strain of genetic hypertension derived from Wistar, administration of various antihypertensive drugs (AHD) during the developmental phase of hypertension (weeks 5-9 of life) prevents the rise of blood pressure. However, only drugs blocking the renin-angiotensin system (RAS, i.e. AT1-antagonist losartan and ACE inhibitor perindopril) have a long-term effect on blood pressure leading to values of systolic blood pressure (SBP) of 174.5+/-14.5 and 169.8+/-15.3 mmHg, respectively, at week 30. At this time, control, untreated PHR have a SBP of 222.0+/-16.6 mmHg (p<0.01 for both groups); age-matched PNR (Prague normotensive rat, bred in parallel with PHR from the same parent pair) exhibit values as low as 123.3+/-11.7 mmHg (p<0.01 from all other values). When losartan was administered to another group of PHR not only at weeks 5-9 but once more at weeks of 15-19 of age, the values of their SBP at week 30 were 156.8+/-12.64 mmHg, i.e., values significantly (p<0.01) different not only from 239.7+/-17.59 mmHg (value of the untreated PHR group) but also from 174.5+/-14.5 mmHg (value of PHR to which losartan was administered only once, at weeks 5-9). Thus, twice repeated administration of losartan in young age almost normalizes blood pressure deep into adult age. Proteinuria, a common finding in adult PHR, is also significantly lower in adult age in both groups receiving at weeks 5-9 drugs blocking RAS; the values at week 30 are 4.0+/-0.26 mg/24 h/rat in the losartan and 3.87+/-0.27 in the perindopril group, in contrast to 12.8+/-1.08 (p<0.01 for both groups) in control PHR. In conclusion, early brief administration (weeks 5-9 of life) of RAS-blocking agents to PHR led to long-term antihypertensive and antiproteinuric effects. These effects were significantly intensified by a second brief administration at weeks 15-19.
 ...
PMID:Long-term effect on blood pressure of early brief treatment by different antihypertensive agents: a study in the prague hypertensive rat. 993 30

Tubular cell damage is an important mediator of interstitial fibrosis in chronic renal diseases. Glomerular and tubular damage in genetic hypertension was therefore studied. Tubular and glomerular damage was investigated in 10-, 40-, and 70-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and compared with glomerular capillary pressure (P(GC)) and glomerulosclerosis in superficial (OC) and juxtamedullary (JMC). Tubular vimentin was used as criterion of tubular damage. Variation in tubular diameter was measured during change in perfusion pressure, and ureter ligation was used to demonstrate the relationship between tubular pressure and appearance of vimentin-positive cells. Tubular and glomerular damage was most pronounced in JMC and greater in SHR than in WKY. It was absent in 10-wk-old WKY and significantly higher in JMC of SHR compared with WKY at 70 wk of age. Numbers of vimentin-positive segments were 18 +/- 9 vs. 38 +/- 7% in JMC of 70-wk-old WKY and SHR (P < 0.02), and glomerulosclerosis was seen in 8 +/- 3 vs. 19 +/- 5% of glomeruli in JMC of 70-wk-old WKY and SHR, respectively (P < 0.01). P(GC) was 45 +/- 3 mmHg in JMC of WKY and 57 +/- 3 mmHg in JMC of 70-wk-old SHR (P < 0.001). Tubular diameter variation was greatest in SHR (P < 0.05) during pressure variation. Proteinuria was present only in 40- and 70-wk-old SHR and did not correlate with tissue damage. Tubular and glomerular damage in both strains develops in parallel and may be caused by a common mechanism, which may be glomerular capillary and tubular wall stretch during acute blood pressure variation which is greatest in JMC in SHR.
 ...
PMID:Glomerular and tubular damage in normotensive and hypertensive rats. 1553 68