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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Venous resistance contributes very little to total peripheral resistance; more than half of the total blood volume, however, is contained in the extrathoracic veins. Owing to marked differences between venous and arterial anatomy and physiology, studies on veins and arteries usually require different methodological approaches. Whereas for arteries the most relevant parameters are resistance, pressure and flow, for veins volume and compliance are most important. For studies of general aspects of the peripheral circulatory system, venous occlusion plethysmography is probably the most useful method. The determination of both the rate of rise in limb volume and the total volume rise after inflating a proximally applied occlusion cuff to a subdiastolic pressure permits the concomitant estimation of both arterial flow and venous compliance. 2. Studies of direct pharmacological or physiological effects on veins, interactions of various pharmacological or physiological stimuli, or pathophysiological changes in venous responsiveness have been facilitated by the development of investigational techniques relying on direct measurements of the compliance of single human veins in vivo. One of these, relying on the use of a linear variable differential transformer (LVDT) for determining changes in the compliance of superficial veins at a standardized congestion pressure, has been found very suitable for the practical application in both patients and healthy subjects. 3. Physiological studies were carried out on the effect of age, exercise, temperature, and the menstrual cycle on venous compliance and venous responsiveness to various stimuli. In addition, interindividual variability in venous responsiveness in monozygotic and dizygotic twins and in unrelated subjects was investigated, and studies on the function of the endothelium were carried out in man in vivo. 4. Pathophysiological studies using this technique were reported from patients with hypertension, orthostatic hypotension, myocardial infarction, varicosis, cystic fibrosis, asthma, diabetes, systemic sclerosis, and cluster headache. 5. Clinical pharmacological studies represent a most important field for the use of this method. Studies were carried out on the effects of a large number of constrictor and dilator agents, and also on drug interactions on human veins in vivo. Venoconstriction was observed after local administration of alpha-adrenoceptor and 5-HT-receptor agonists, ergot derivatives, angiotensinogen, angiotensin I and II, and several prostaglandins. 6. Owing to the low venous tone present under effects can usually be quantified only on veins e.g. noradrenaline or 5-hydroxytryptamine. Under these conditions dilatation was observed after the administration of beta-adrenoceptor agonists, cholinergic (muscarinic) agonists, nitrates, calcium antagonists, bradykinin, substance P and several prostaglandins.
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PMID:Clinical pharmacology, physiology and pathophysiology of superficial veins--1. 782 19

To determine the effect of diabetes on the cardiac renin-angiotensin system, we compared angiotensin II binding density and renin, angiotensinogen, and type 1 angiotensin II (AT1) receptor mRNA levels in hearts of Sprague-Dawley rats 14 days after the administration of streptozotocin (STZ), in vehicle-treated control rats, and in STZ-administered rats made euglycemic with insulin. Myocardial angiotensin II receptor density, determined using an in situ autoradiographic technique, was increased significantly in hyperglycemic diabetic rats in comparison with control rats and euglycemic diabetic rats (P < 0.01) as a result of an increase in both AT1 and AT2 (type 2 angiotensin II) subtypes. The myocardial AT1 receptor mRNA level, determined by slot blot hybridization, was also significantly greater in the hyperglycemic diabetic rats (P < 0.005). Neither plasma renin concentration nor cardiac renin or angiotensinogen mRNA levels differed among the three study groups. In an additional experiment, control and diabetic rats were infused with angiotensin II (200 ng.kg-1.min-1 i.p. for 7 days) or vehicle. Plasma renin concentration decreased significantly, whereas no significant changes occurred in cardiac renin or angiotensinogen steady-state mRNA levels. As in the first experiment, levels of AT1 receptor mRNA were significantly greater in the diabetic rats. Thus, myocardial angiotensin II receptor density is increased in diabetic rats in association with an increase in steady-state AT1 receptor mRNA levels, an abnormality that appears to be independent of changes in the circulating renin-angiotensin system.
Diabetes 1994 Oct
PMID:The cardiac renin-angiotensin system in STZ-induced diabetes. 792 85

It has been hypothesized that the renin-angiotensin system plays a pathophysiologic role in the renal hemodynamic abnormalities that occur in diabetes mellitus and thereby contributes to the development of diabetic nephropathy. In this study, the tissue-specific regulation of renin and angiotensinogen mRNA levels and the abundance of glomerular angiotensin II receptors were examined in male Sprague-Dawley rats (160 to 240 g) made diabetic with streptozotocin. One subgroup of diabetic rats remained untreated, whereas a second diabetic subgroup received twice-daily doses of insulin to ameliorate hyperglycemia. Animals were euthanized 2 wk after the induction of diabetes. Mean plasma glucose levels at the time of euthanasia were significantly elevated in the untreated diabetic animals when compared with controls or insulin-treated diabetic rats. Weight gain was similar in control and insulin-treated diabetic rats, whereas the untreated diabetic rats gained significantly less. Plasma renin concentration did not differ between control, diabetic, and insulin-treated diabetic groups. In the kidney, no significant differences were found in either angiotensinogen or renin mRNA levels in diabetic animals, whereas glomerular angiotensin II receptors were significantly less abundant in untreated rats as compared with control or insulin-treated diabetic subgroups. Angiotensinogen mRNA levels were significantly lower in the livers and adrenals of diabetic rats in comparison to those in controls and insulin-treated diabetic rats, whereas angiotensinogen mRNA levels in the brain remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The renin-angiotensin system in streptozotocin-induced diabetes mellitus in the rat. 813 Mar 60

Recently, the obese Zucker rat (OZR), an animal model of non-insulin-dependent (type II) diabetes, was shown to respond to converting enzyme inhibition with decreased albuminuria and a marked attenuation of glomerular injury. It was hypothesized that the OZR would possess low plasma renin values and an increased vascular responsiveness to angiotensin II, and therefore, the renin-angiotensin system (PRA, active renin, inactive renin, renal renin content, and plasma angiotensinogen) and vascular reactivity in OZR at 10 and 24 wk of age were investigated. PRA and renin concentration, inactive plasma renin, and renal renin content were all significantly (P < 0.05) reduced in OZR when compared with age-matched lean controls. The ratio of inactive to total renin was significantly increased in the OZR. OZR aortic ring vascular reactivity to KCl, norepinephrine, and angiotensin II was assessed. Despite essentially equal or increased contractile responses to KCl and norepinephrine at both 10 and 24 wk of age, the OZR was not more sensitive to angiotensin II and displayed a significantly reduced contractile response to angiotensin II at 24 wk of age, when compared with lean age-matched controls. It was concluded that the renal protective effect of converting enzyme inhibition in OZR, despite significantly reduced PRA and concentration, inactive plasma renin, and renal renin content, may not be due to a diabetes-induced increased vascular reactivity to angiotensin II.
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PMID:The renin-angiotensin system in the type II diabetic obese Zucker rat. 813 Mar 62

Recent evidence indicates a role for the renin-angiotensin system (RAS) in the pathogenesis of glomerular injury in diabetes. To further explore the RAS in diabetes, studies were conducted in nondiabetic control rats and in moderately hyperglycemic diabetic (DM) rats. In DM rats, both acute and chronic therapy with the specific angiotensin II (ANG II) receptor antagonist losartan did not affect glomerular hyperfiltration or hyperperfusion but selectively normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. To determine the basis of intrarenal hemodynamic responsiveness to RAS inhibition, we conducted biochemical, molecular biological, and immunohistochemical studies to assess endogenous RAS activity. Values for plasma renin concentration and serum angiotensin-converting enzyme (ACE) activity in DM rats were normal. In contrast, intrarenal renin protein content, and renin and angiotensinogen mRNAs, were increased in DM rats, suggesting disproportionate activation of the intrarenal RAS. Total renal ACE activity was significantly reduced in DM rats, but immunohistochemical studies indicated redistribution of ACE in the diabetic kidney. Proximal tubule ACE activity was reduced, but ACE immunostaining intensity was enhanced in glomeruli and renal vasculature. Together, these observations indicate increased RAS activity in those sites (glomeruli and vasculature) most likely to regulate hemodynamic function, potentially explaining the prominent responses to pharmacological blockade of ANG II formation and/or action.
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PMID:Renal renin-angiotensin system in diabetes: functional, immunohistochemical, and molecular biological correlations. 823 77

The genetic and environmental determinants of hypertension, lipid abnormalities, and coronary artery disease (CAD) have been studied for 15 years in Utah in population-based multigenerational pedigrees (2500 subjects among 98 pedigrees), twin pairs (74 monozygous and 78 dizygous), hypertensive siblings (131 sibships), siblings with CAD before age 55 (45 sibships), and anecdotally ascertained pedigrees with type II diabetes (271 subjects among 16 pedigrees), lipoprotein lipase deficiency (106 subjects in a single pedigree), and familial hypercholesterolemia (502 heterozygotes among 50 pedigrees). Estimates of heritability ranged from 20 to 75% for blood pressures and blood lipids. A strong positive family history predicts a future occurrence of hypertension (relative risk [RR] = 3.8) and CAD (RR = 12.7). Segregating single-gene effects were found for several 'intermediate phenotypes' associated with hypertension (erythrocyte sodium-lithium countertransport, intraerythrocytic sodium, a relative fat pattern, total urinary kallikrein excretion, and fasting insulin levels). Strong single-gene effects in segregation analysis were also found for low-density lipoprotein (LDL) cholesterol, lipoprotein (a) (Lp[a]), low high-density lipoprotein (HDL) cholesterol, and high apolipoprotein (apo) B. Deoxyribonucleic acid (DNA) markers of lipid abnormalities or hypertension have included LDL-receptor defects, lipoprotein lipase deficiency, high Lp(a), familial defective apo B, decreased quantitative levels of apo B, apo E phenotype, angiotensinogen, and 'glucocorticoid remediable aldosteronism (GRA) hypertension.' Also tested in Utah studies, but not found to be DNA markers for hypertension, were the genetic loci for the structural genes for renin and angiotensin-converting enzyme, and the sodium antiport system. In addition, important gene-gene interactions (LDL receptor with apo E2) and gene-environment interactions (kallikrein with potassium intake) were found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetic basis of familial dyslipidemia and hypertension: 15-year results from Utah. 829 39

In this article, we have discussed the localization of components of the renal renin-angiotensin system, as well as the existing information on the regulation of this axis and the effects of Ang II on renal function. All the components of the renin-angiotensin system are present in both fetal and adult kidney. In the adult kidney, renin is principally localized to jg cells of the distal afferent arteriole, where release is stimulated by increases in intracellular cAMP and inhibited by increases in cytosolic calcium. Four distinct stimuli mediating renin release are (1) NaCl sensed at the macula densa, (2) the sympathetic nervous system, (3) humoral factors, with Ang II, vasopressin, endothelin, and adenosine inhibiting renin release, and (4) changes in intrarenal blood pressure. Alterations in renal renin gene expression have been reported in pathophysiological states, such as salt depletion, diabetes mellitus, ureteral obstruction, Bartter's syndrome, and with high protein feeding. The highest renal concentrations of mRNA for the renin substrate angiotensinogen are found in the PT, where the protein is localized to subapical granules. Both salt depletion and androgens upregulate renal angiotensinogen mRNA. Of interest, renal angiotensinogen mRNA levels are lower in SHR than in normotensive WKY rats. As with angiotensinogen, renal ACE is mainly localized to the PT, with highest concentration on the brush border. The mechanisms of regulation of both renal angiotensinogen and ACE require further study. Using recently developed specific nonpeptide Ang II receptor antagonists, it appears that adult renal Ang II receptors are principally of the AT1 class, whereas fetal kidney Ang II receptors are of the AT2 subtype. By binding to AT1 receptors, Ang II exerts constrictive effects on both afferent and efferent arterioles, with increased effect reported on efferent arterioles. Glomerular Ang II receptors are localized to mesangial cells, mediating contractile responses resulting in changes in glomerular surface area and Kf, and potentially regulating mesangial sieving and phagocytosis. These receptors are reduced with salt restriction or in experimental diabetes. The highest concentrations of tubular Ang II receptors are found in PT, on both brush border and basolateral membranes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The intrarenal renin-angiotensin system. 843 83

Genotypic abnormalities of the renin-ANG system have been suggested as a risk factor for the development of diabetic nephropathy. Cleavage of angiotensinogen is the rate-limiting step in the activation of the renin-ANG system. The TT genotype of a polymorphism encoding threonine instead of methionine (M235T) has been associated not only with increased plasma angiotensinogen concentration but also with essential hypertension. In addition, a polymorphism in the angiotensinogen gene substituting methionine for threonine (T174M) has been associated with hypertension in nondiabetic populations. We studied the relationship between these polymorphisms in the angiotensinogen gene in IDDM patients with diabetic nephropathy (121 men, 74 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years). There was no difference in M235T genotype distribution between IDDM patients with diabetic nephropathy and those with normoalbuminuria: 73/97/25 (37/50/13%) vs. 67/95/23 (36/52/12%) had MM/MT/TT genotypes, respectively. No difference in distribution of T174M genotypes between nephropathic and normoalbuminuric IDDM patients was observed either: 148/44/1 (77/23/0.5%) vs. 141/42/2 (76/23/1%) had TT/TM/MM genotypes, respectively. In patients with nephropathy, systolic blood pressure was higher (161 +/- 22 mmHg [mean +/- SD]) in patients carrying TT genotype of the M235T angiotensinogen polymorphism as compared with patients with MM or MT genotypes (150 +/- 23 mmHg; P = 0.03). We conclude that neither the M235T nor the T174M polymorphism in the angiotensinogen gene contributes to genetic susceptibility to diabetic nephropathy in white IDDM patients, whereas the TT genotype of the M235T is associated with elevated blood pressure in patients with diabetic nephropathy.
Diabetes 1996 Mar
PMID:Angiotensinogen gene polymorphisms in IDDM patients with diabetic nephropathy. 859 44

To investigate predictive genetic markers for diabetic nephropathy, we studied the genetic polymorphisms of angiotensin-converting enzyme (ACE) and angiotensinogen (AGN) in Japanese subjects with non-insulin-dependent diabetes mellitus (NIDDM) with and without nephropathy. Genotype distributions were studied in 132 unrelated NIDDM patients of three groups with normoalbuminuria ([Normo] n = 53), microalbuminuria ([Micro] n = 54), and macroalbuminuria ([Macro] n = 25). The ACE insertion/deletion (I/D) polymorphism of intron 16 was identified by polymerase chain reaction, and the AGN M235T polymorphism was identified by restriction fragment length polymorphism analysis. There were no significant associations between AGN 235 allele or genotype and diabetic nephropathy. The D allele of ACE was significantly more frequent in the Micro (P = .003) and Macro (P = .009) group than in the Normo group. Overall frequencies of the ACE genotype did not differ significantly between the Micro and Macro groups. There were significant relationships between I/D polymorphism and plasma ACE activity; the DD genotype had the highest activity. A multiple logistic regression analysis revealed that the D allele is a strong and independent risk factor for abnormal albuminuria in NIDDM patients. These results suggested that ACE I/D polymorphism, but not AGN M235T polymorphism, is a possible genetic risk factor for diabetic nephropathy in Japanese NIDDM patients.
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PMID:Association analyses of the polymorphisms of angiotensin-converting enzyme and angiotensinogen genes with diabetic nephropathy in Japanese non-insulin-dependent diabetics. 859 93

The allele 235T (a threonine in place of a methionine at position 235) of angiotensinogen has been found to be associated with a predisposition to essential hypertension. We investigated whether this allele also confers increased susceptibility to nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). A group of 380 patients who had had IDDM for 15 to 20 years were genotyped at the angiotensinogen 235 locus. Included were 75 patients with normoalbuminuria (albumin excretion rate < 30 micrograms/min), two series of patients with microalbuminuria (n = 30 and n = 136), and two series with overt proteinuria (n = 41 and n = 98). Allele 235T frequency was higher among cases with microalbuminuria (0.41 in the two series combined) or overt proteinuria (0.40) than in the normoalbuminuria group (0.36). However, this difference was not statistically significant with this sample size (chi 2 = 1.2, P = NS with 2 df). Under a recessive model, allele 235T homozygotes had a 1.6-fold risk of developing nephropathy relative to carriers of other genotypes, but this value was not significantly different from 1(95% CI = 0.8 to 3.5). The strength of the association did not improve after stratification by degree of glycemic control. With respect to the hypertension in these IDDM patients, no association with allele 235T was found. Allele 235T frequencies in normotensive and hypertensive individuals were 0.363 and 0.353, respectively, among normoalbuminuric IDDM individuals (chi 2 = 0.01, P = NS) and 0.411 and 0.414 among microalbuminuric IDDM subjects (chi 2 = 0.0, P = NS). We conclude that the angiotensinogen polymorphism M235T might influence susceptibility to nephropathy in insulin-dependent diabetes, but its effect, if any, is rather small and independent of hypertension.
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PMID:Angiotensinogen polymorphism M235T, hypertension, and nephropathy in insulin-dependent diabetes. 862 Dec 7


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