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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper attempts to define the theory and practice of a modern approach to the initial workup of the patient with hypertension. The process includes a complete general medical evaluation along with special measures to enable the fullest characterization and clinical differentiation of the disease. The initial workup aims to (a) establish that the hypertension is sustained and should be treated; (b) identify all definable and curable causes for the hypertension; (c) identify the presence and degree of attendant risk factors such as smoking, alcohol use, obesity, diabetes, and abnormal lipid metabolism; (d) characterize the hypertension in terms of its pathophysiology; and (e) assess the presence and degree of target organ damage to the heart, brain, and kidneys. Because all diastolic hypertension is due to arteriolar vasoconstriction, a fundamental strategy of this process is to distinguish between renin-mediated and sodium-related vasoconstrictive forces and to evaluate which is preponderant. The chief instruments of this strategy are the renin-sodium profile and the response of plasma renin activity and blood pressure to specific antirenin system drugs. The captopril test, an important protocol in making this distinction, is primarily a powerful screening tool for confirming the possible presence or absence of curable renovascular disease or curable primary aldosteronism. That renin profiling cannot accurately discriminate between the contributions of either the renin or sodium-volume factors in that large fraction of medium-renin patients is not a viable reason for not performing the test. The test has its greatest strength for identifying sizable numbers of otherwise unrecognizable patients with very high or very low renin concentrations who might have curable disorders and who likely reflect different pathophysiologic vasoconstrictive mechanisms for which entirely different drug therapies are appropriate. However, the baseline renin test is also useful for assessing prognosis and the likelihood of a heart attack and it is valuable for deciding whether to use an anti-renin system drug (for medium and high renin concentrations) as opposed to natriuretic agents (low-renin patients) such as a diuretic or calcium antagonists as the primary step. In our present state of knowledge, the basic diagnostic biochemical workup includes the renin-sodium profile and the 24-h urinary sodium, potassium, and microalbumin excretion rates. This package is further enriched by baseline electrocardiography and echocardiography and the evaluation of glucose and lipid patterns.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical evaluation and differential diagnosis of the individual hypertensive patient. 191 3

We have investigated 975 different grazing sections of vessels in kidney preparations of 20 rats of the Wistar strain. Half of these genetically identical animals had an insulin-deficiency diabetes induced by injection of streptozocin. The kidneys were removed for investigation after 2 and 12 weeks duration of diabetes. The vessel cross-section, wall, lumen and endothelial surface area were determined in renal arteries, arterioles and preglomerular afferent arterioles in a blind experiment. Statistically detecteable changes were found in the diabetic vessels in the early stage of the diabetes. Preglomerular afferent arterioles showed a highly significant and increasing lumen dilatation commencing after 2 weeks. Diabetic arteries and arterioles developed narrower lumina. A significant thickening of the endothelium took place at the same time in both vessel types. All three vessel regions became smaller and had thinner walls than healthy vessels as the diabetes progressed. The findings on the afferent vessels indicate that haemodynamic effects on the glomerulus are to be expected. Familial diabetic gloermulopathy begins with a reversible hyperfiltration. However, the mechanism has not been clarified in the context of the diabetic metabolic disorder, and this change is probably the haemodynamic consequence of the substantial dilatation of the preglomerular afferent arterioles. With their renin-positive segment, these arterioles are the centre of intrarenal regulation. The increase of the capillary glomerular pressure associated with the dilatation of the preglomerular afferent arterioles is a crucial factor in the development of diabetic glomerulopathy.
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PMID:Morphometric investigations on intrarenal vessels of streptozotocin-diabetic rats. 192 64

The pathogenesis of diabetic nephropathy remains elusive. A role for renal prostaglandins in antagonizing the hormonal effects of renin-angiotensin II has been postulated as a putative factor leading to hyperfiltration in patients with Type 1 (insulin-dependent) diabetes mellitus. Our aim was to elucidate the effects of angiotensin II on kidney haemodynamics and on blood pressure in eight normal subjects, in nine normotensive, in nine hypertensive with normal sodium-lithium countertransport activity in erythrocytes, in seven hypertensive without and in eight hypertensive Type 1 diabetic patients with microalbuminuria and with high sodium-lithium countertransport activity in erythrocytes. Angiotensin II infusion (4 ng.kg-1.min-1 for 60 min) decreased the glomerular filtration rate to a greater extent in normal subjects (-20%), than in normotensive patients (-5% p less than 0.01), in hypertensive patients with normal sodium-lithium countertransport activity in erythrocytes (-8% p less than 0.01) in hypertensive patients with high sodium-lithium countertransport (-6% p less than 0.01) and in hypertensive microalbuminuric patients (-5% p less than 0.01) with Type 1 diabetes. The urinary excretion rate of vasodilatory prostaglandins was two-three fold higher in all patients than in normal subjects. Acute indomethacin treatment restored a normal response to angiotensin II infusion in normotensive patients, but did not change the renal haemodynamic response in normal subjects. With regard to hypertensive patients with and without microalbuminuria indomethacin treatment restored a normal response to angiotensin II in some but not all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired response to angiotensin II in type 1 (insulin-dependent) diabetes mellitus. Role of prostaglandins and sodium-lithium countertransport activity. 193 64

Plasma renin activity was measured in ten diabetics with nephropathy, 10 uncomplicated diabetics and 10 normal healthy controls. All the groups were comparable for age, sex, and duration of diabetes. Plasma renin activity was found to be significantly lower in patients with nephropathy in comparison to uncomplicated diabetics and normal healthy controls. There was no correlation between plasma renin activity and mean blood pressure or degrees of renal failure. These findings raise the possibility that microangiopathic changes occurring in the glomeruli and juxta-glomerular apparatus may alter the renin-angiotensin system. Also the finding of low renin in diabetics with nephropathy may modify management policies.
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PMID:Plasma renin activity in diabetics with and without microangiopathy. 830 32

Blood pressure is generally normal in insulin-dependent diabetic patients in the absence of nephropathy. Despite this, exchangeable sodium is increased. Blood pressure rises with the development of incipient nephropathy, and hypertension is common in patients with overt nephropathy. Exchangeable sodium is then markedly increased, but plasma renin is not suppressed. Raised BP in diabetic nephropathy is probably sustained, in part at least, by sodium retention and inappropriate activity of the renin-angiotensin system. There is an increased prevalence of hypertension among patients with non-insulin-dependent diabetes (NIDDM). In normotensive patients, exchangeable sodium is elevated and plasma renin is suppressed. In hypertensive patients, exchangeable sodium is less markedly increased, while plasma renin is again suppressed. These findings are in contrast with those in diabetic nephropathy, and are in keeping with the hypothesis that hypertension in NIDDM is usually due to coexisting essential hypertension. Also in keeping with this suggestion is an increased prevalence of raised BP among the siblings of NIDDM patients. Prolonged hyperinsulinaemia precedes the diagnosis of NIDDM, and hypertension is often present at the time of diagnosis. Insulin resistance and compensatory hyperinsulinaemia might lead to an increase in BP by a number of putative mechanisms, such as enhancing renal sodium retention, by an effect on cell membrane ion exchange mechanisms or by enhancing activity of the sympathetic nervous system. This seems a fertile area for further research, although a causal link between insulin resistance and hyperinsulinaemia on the one hand, and raised BP on the other, remains to be proved.
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PMID:The causes of raised blood pressure in insulin-dependent and non-insulin-dependent diabetes. 195 22

We studied whether or not neonatal streptozotocin (STZ) treatment would alter mean arterial pressure (MAP) and blood pressure regulating factors in conscious and unrestrained spontaneously hypertensive rats (SHR). Neonatal STZ administration to SHR resulted in type 2 diabetes mellitus with reduced MAP and heart rate. Plasma glucose was markedly increased in these diabetic animals and was inversely correlated with MAP. In the diabetic SHR, the hypotensive responses to captopril (SQ) or enalapril, administered intravenously, were diminished, regardless of preceding administrations of vasopressin V1-antagonist (AVPA) or hexamethonium (C6), when compared to findings in control rats. In contrast, the C6-induced hypotension was similar in rats with diabetes and control animals. AVPA led to no decrease in MAP in either group. Hypotensive responses to SQ following AVPA and C6 inversely correlated with the plasma levels of glucose in the diabetic group. The combined blockade of the renin-angiotensin system (RAS), sympathetic nervous system and vasoconstrictive action of vasopressin (AVP) abolished the differences in MAP between the groups. Pressor and bradycardic responses to intravenous noradrenaline, angiotensin II and AVP were practically identical in the diabetic and control SHR. Urinary aldosterone excretion rate was not altered by neonatal STZ treatment. In conclusion, a decrease in MAP in SHR with neonatal STZ treatment may be attributed to the suppressed pressor activity of RAS.
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PMID:Suppression of the renin-angiotensin system induced by streptozotocin treatment in neonatal spontaneously hypertensive rats. 197 12

Chronic renal insufficiency is a progressive, self-perpetuating process which is influenced in part by activation of the intrarenal renin-angiotensin system. Oral angiotensin-converting enzyme inhibitors are being studied in animals and humans to determine whether they slow the decline in renal function characteristic of progressive renal disease. In animals that have reduced renal mass, streptozotocin-induced diabetes mellitus, or puromycin aminonucleoside nephrosis, these agents can reduce proteinuria, decrease the frequency of sclerotic glomeruli, and normalize intrarenal hemodynamics. They also may decrease glomerular hypertrophy that occurs after renal ablation. In human trials, angiotensin-converting enzyme inhibitors decrease proteinuria by altering the glomerular capillary permeability. The effect of these agents on progressive disease may be influenced by how soon therapy is begun and how long it is continued.
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PMID:Use of angiotensin-converting enzyme inhibitors in chronic progressive renal disease. 202 23

Epidemiological evidence suggests that there is a close association between obesity, non-insulin-dependent diabetes (NIDDM) and hypertension. Obesity and NIDDM are the classical insulin-resistant states. Even in the absence of these conditions, essential hypertension is associated with insulin resistance. In view of the acute effects of insulin on renal sodium reabsorption, the sympathetic nervous system, the renin-angiotensin-aldosterone system, the transmembranous cation transport, the cardiovascular reactivity, the atrial natriuretic peptide and the kallikrein-kinin system, hyperinsulinaemia may contribute to the development of hypertension in these diseases. Preliminary evidence suggests that sensitivity to these possible blood-pressure-elevating action(s) of insulin is still present despite the resistance to the glucose-lowering action of the hormone. However, extrapolation of the epidemiological data and results of acute experiments indicate that the impact on blood pressure is rather small. The pathophysiological mechanisms of hypertension in the above-mentioned conditions are also not always consistent with insulin action(s). Moreover, some data suggest that insulin resistance, and not hyperinsulinaemia per se, underlies the blood pressure elevation, while the possibility cannot be excluded that both hypertension and insulin resistance are co-inherited, but unrelated, abnormalities.
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PMID:Insulin and blood pressure regulation. 204 23

The common association between diabetes mellitus and hypertension may be promoted by several mechanisms. Patients with insulin-dependent (type I) diabetes and prone to develop nephropathy often have a familial predisposition for essential hypertension, whereas normotensive healthy offspring of nondiabetic essential hypertensive parents tend to have a reduced insulin sensitivity and increased plasma insulin levels. Na+ retention occurs as a characteristic alteration in type I or non-insulin-dependent (type II) diabetes; exchangeable body Na+ (Naex) is increased by 10% on average. This abnormality develops in the uncomplicated stage of diabetes and differentiates diabetic from nondiabetic essential hypertensive subjects. Possible Na(+)- retaining mechanisms include increased glomerular filtration of glucose leading to enhanced proximal tubular Na(+)-glucose cotransport, hyperinsulinemia (which activates several tubular Na+ transporters), an extravascular shift of fluid with Na+, and, once it occurs, renal failure. The pathogenetic role of Na+ retention in diabetes-associated hypertension is supported by positive correlations between systolic or mean blood pressure and Naex and by normalization of blood pressure after removal of excess Na+ by diuretic treatment in hypertensive diabetic subjects. The latter may also have an enhanced sensitivity of blood pressure to Na+. Plasma levels of active renin, angiotensin II, aldosterone, and catecholamines are usually normal or low in metabolically stable type I or type II diabetes. However, an exaggerated vascular reactivity to norepinephrine and angiotensin II commonly occurs already at uncomplicated stages of type I or type II diabetes. This may be a manifestation of functional (i.e., intracellular electrolytes) and/or morphological (proliferation, narrowing, and stiffening) vasculopathy. Diabetes-associated Na+ retention, vasculopathy, and a presumably inherited predisposition for both diabetes and essential hypertension may represent important complementary factors favoring the frequent occurrence of hypertension in the diabetic population.
Diabetes Care 1991 Mar
PMID:Central role of sodium in hypertension in diabetic subjects. 204 37

This paper synthesizes the pathogenic steps of arterial hypertension in diabetes mellitus: hyperosmolarity due to the hyperglycemia and increased sodic tubular reabsorption accounting for the expansion of the extracellular volume with hypervolemia; abnormalities of the ionic membrane pumps leading to abnormal intracellular calcium distribution, thereby inducing an increased vascular tone; atypical vasomotor reactivity to cathecolamines; modifications of the renin-angiotension-aldosterone system. The pathophysiological derangements by which hypertension could induce nephropathy are examined: the vasodilatation which can be detected from the onset of diabetes, may be a determinant in the transmission of systemic hypertension to the glomerular microcirculation with resulting enhancement of the hydrostatic transglomerular pressure gradient (i.c. the major factor producing glomerular injury), glomerular plasmatic flow and filtration rate. The nephron hyperfiltration increases the movement of plasmatic proteins across the glomerular capillary wall with subsequent mesangial hyperactivity and sclerosis. Antihypertensive treatment in diabetes follows general guidelines and it should be instituted even in the case of microhypertension being facilitated in this setting the appearance of microalbuminuria i.e. the starting point of nephropathy. Even if experimental studies are to favor ACE inhibitors as the first-line drugs for abating glomerular hypertension by mitigation of the direct effect of angiotensin II on the efferent arteriolar tone, clinical observations suggest that, regardless of type of treatment, the normalization of systemic arterial pressure, by reversing glomerular hypertension may be effective in preventing diabetic nephropathy.
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PMID:[The pathogenesis of arterial hypertension in diabetes mellitus and its role in nephropathy]. 207 80


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