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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intra-arterial pressure was recorded continuously in 26 patients with uncomplicated essential hypertension under standardized conditions. Recordings were analyzed beat by beat to obtain mean pressures and variability, expressed as the standard deviation of the frequency histogram. The major factors influencing variability were the level of pressure and the intensity of physical activity; systolic variability increased with progressive impairment of sino-aortic baroreflexes. Diastolic pressure increased with the level of sympathetic activity as reflected by plasma norepinephrine levels. After allowance for the decrease of plasma renin activity (PRA) with age, direct relationships were observed between PRA (log values) and the level of pressure and systolic variability; plasma angiotensin II values did not correlate. Systolic variability increased with the systolic response to cold but was unrelated to the response to dynamic or isometric exercise. Variability also tended to increase with obesity and was unrelated to age, sex, or race.
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PMID:Factors determining direct arterial pressure and its variability in hypertensive man. 699 60

Several blood-pressure-regulating factors including exchangeable sodium, blood volume, plasma renin, aldosterone, norepinephrine (NE), and epinephrine (E) levels, urinary catecholamine excretion rates, and cardiovascular responsiveness to infused NE and angiotensin II (AII) were compared among age-matched subgroups of normal subjects (15 with normal weight, 15 with overweight) and patients with essential hypertension (15 with either normal weight, overweight, or obesity). Exchangeable sodium, blood volume, plasma and urinary sodium and potassium, plasma renin, aldosterone and epinephrine levels, and NE or E excretion rates did not differ significantly among the five subgroups. Minimal differences included a slightly higher heart rate in overweight patients than in overweight normal subjects (p less than 0.01) and a tendency for a higher plasma NE in overweight than in normal weight patients. Plasma NE obtained immediately before NE infusion as well as the plasma clearance of NE did not differ among the five subgroups except, however, for a somewhat low NE clearance in obese patients. The NE pressor dose tended to be lower in normal-weight hypertensive than in normal-weight normotensive subjects. No alteration was apparent in overweight or obese hypertensive patients. Pressor responses to AII were similar in the different subgroups. These findings suggest that overweight does not confer a unique aberration in the body sodium-volume state, circulating renin, aldosterone or catecholamines, or cardiovascular responses to NE or AII which result in hypertension.
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PMID:Pressor factors and cardiovascular pressor responsiveness in lean and overweight normal or hypertensive subjects. 704 22

Left ventricular hypertrophy (LVH) is an early complication of hypertension. To a certain degree, this process counteracts the parietal stress induced by high blood pressure. Genetic factors, obesity, high salt diet and different growth factors, notably angiotensin II and noradrenaline, can also predispose to hypertrophic cardiomyopathy. Left ventricular mass is increased on echocardiography in about 20% of hypertensive subjects. LVH is initially associated with a change in myocardial diastolic function and later with abnormal systolic function. It is a major risk factor, a cause of cardiac failure, reduction in coronary reserve and of ventricular arrhythmias. Treatment of hypertension is associated with regression of LVH and preservation or improvement in myocardial diastolic and systolic functions. The decrease in left ventricular mass could reduce the incidence of cardiovascular complications in hypertension.
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PMID:[Physiopathology of left ventricular hypertrophy]. 764 13

Resistance to the metabolic effects of insulin and compensatory hyperinsulinemia have been postulated to mediate human essential hypertension, especially when associated with obesity. Evidence supporting this hypothesis has come mainly from epidemiological studies showing correlations between insulin resistance, hyperinsulinemia, and blood pressure, and from short-term studies suggesting that insulin has renal and sympathetic effects that could raise blood pressure if the effects were sustained. However, there have been no studies demonstrating a direct causal relationship between chronic hypertension and insulin resistance or hyperinsulinemia in humans. The few long-term studies that have been conducted in dogs and humans do not support the hypothesis that hyperinsulinemia causes hypertension or potentiates the hypertensive effects of other pressor agents such as angiotensin II or increased adrenergic tone. To the contrary, multiple studies in dogs and in humans suggest that the vasodilator action of insulin tends to reduce blood pressure. Although resistance to insulin's metabolic effects has been suggested to be essential for hyperinsulinemia to cause hypertension, chronic increases in plasma insulin concentrations do not cause hypertension in dogs or humans even in the presence of insulin resistance. Also, recent studies have also shown that the blood pressure-lowering effects of antihyperglycemic agents, initially believed to lower blood pressure by decreasing insulin resistance, may be unrelated to their effects on insulin sensitivity. Obesity appears to be a key factor in accounting for correlations between insulin resistance, hyperinsulinemia, and hypertension, but increased blood pressure in obesity does not appear to be mediated by insulin resistance and hyperinsulinemia. Although insulin resistance and hyperinsulinemia may not be directly linked to hypertension, there is increasing evidence that metabolic abnormalities associated with insulin resistance may increase the risk of cardiovascular disease (e.g., coronary artery disease) associated with hypertension and Type II diabetes. For this reason, further studies of the long-term effects of insulin resistance on cardiovascular, renal, and metabolic functions are needed.
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PMID:Insulin resistance, hyperinsulinemia, and hypertension: causes, consequences, or merely correlations? 770 Aug 80

We have previously shown that insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle cell (VSMC) Ca(2+)-ATPase mediated Ca2+ efflux and vascular relaxation. We have now sought to determine if VSMC from insulin resistant (Zucker Obese, ZO) rats manifest exaggerated [Ca2+]i responses to pressor agonists and impaired [Ca2+]i recovery (rate of [Ca2+]i return to baseline) compared to their lean controls (ZL). Thoracic aortae from ZO and ZL were enzymatically digested to release VSMC (n = 16 animals/group and 8 determinations/group). Freshly dispersed cells were washed, counted, and loaded with Fura-2-AM. The [Ca2+]i responses to and rate of recovery from angiotensin II (AII; 200 nmol/L) and arginine vasopressin (AVP; 10 mumol/L) were studied fluorometrically in stirred suspension (10(6) cells/mL). Peak [Ca2+]i responses to AVP were not significantly different in ZO v ZL, while responses to AII were higher in ZL ([Ca2+]i, 180 +/- 7 v 160 +/- 4% of baseline in ZL and ZO, P < .02). Since we have recently shown insulin to increase AII-releasable Ca2+ stores in sarcoplasmic reticulum, this increase in peak [Ca2+]i response to AII in ZL may reflect relative VSMC insulin resistance in ZO. Despite their increased peak AII response, ZL exhibited a more rapid recovery from both the AII-stimulated load (recovery rate, 66.1 +/- 8.9 v 42.1 +/- 9.0 nmol/L/min in ZL and ZO, P < .02) and the AVP-stimulated [Ca2+]i load (22.2 +/- 2.3 v 18.4 +/- 4.6 nmol/L/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired recovery of vascular smooth muscle intracellular calcium following agonist stimulation in insulin resistant (Zucker obese) rats. 834 33

Angiotensin II exerts its action via at least two distinct receptor subtypes designated AT1 and AT2. AT1 receptors seem to be responsible for most of the known angiotensin II effects while the role of AT2 receptors is not yet clear. Adipocytes of adult rats express exclusively the AT1 subtype. Angiotensin II stimulates prostacyclin release in adult rat adipocytes and in mouse preadipocytes. In the latter prostacyclin release is completely blocked by an AT2 receptor antagonist. Adipocyte angiotensin II receptors seem to be regulated by age and fat mass. Blockade of these receptors by an AT1 antagonist seems to prevent adipose tissue hypertrophy. Moreover, adipose tissue contains all the main components of the renin-angiotensin system such as angiotensinogen, angiotensin converting enzyme, angiotensin II and angiotensin II receptors. Angiotensinogen expression in adipocytes is stimulated by a high fat diet concurrent with enlargement of fat mass, associated with insulin resistance. Angiotensin converting enzyme inhibitors improve insulin sensitivity. Taken together, there is evidence of interaction between insulin and angiotensin II in regulation of adipose tissue metabolism and cellularity. Clarification of these interactions could lead to significant progress in pharmacological treatment of obesity and its comorbidity.
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PMID:The role of angiotensin II and its receptors in regulation of adipose tissue metabolism and cellularity. 878 38

We designed our studies to determine whether blood pressure is elevated in obese Zucker rats compared with lean control rats and to test the importance of the renin-angiotensin and adrenergic nervous systems in long-term blood pressure control in this genetic model of obesity. We monitored mean arterial pressure 24 hours per day using computerized methods in 13- to 14-week-old lean and obese Zucker rats maintained on a fixed, normal sodium intake (3.3 mmol/d). Mean arterial pressure (average of 5 days) was higher in obese (100 +/- 1 mm Hg) than in lean (86 +/- 1) rats. Although control plasma renin activity was lower in obese than in lean rats (3.66 +/- 0.15 versus 5.48 +/- 0.11 ng angiotensin I/mL per hour), blood pressure sensitivity to exogenous angiotensin II was greater in obese than in lean rats. Blockade of endogenous angiotensin II receptors with losartan (10 mg/kg per day) for 7 days also caused a greater decrease in blood pressure in obese (36 +/- 2 mm Hg, n = 6) than in lean (25 +/- 1, n = 5) rats. However, combined alpha- and beta-adrenergic blockade with terazosin (10 mg/kg per day) and propranolol (10 mg/kg per day), respectively, for 8 days caused only modest decreases in blood pressure in obese (9 +/- 3 mm Hg, n = 8) and lean (4 +/- 2, n = 6) rats, despite effective alpha- and beta-adrenergic blockade. These results suggest that increased arterial pressure in obese Zucker rats depends in part on angiotensin II. However, additional mechanisms may also contribute to increased blood pressure in obese Zucker rats.
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PMID:Hypertension in obese Zucker rats. Role of angiotensin II and adrenergic activity. 895 95

Synthesis of angiotensin II (ANG II) has recently been described in adipose cells and has been linked to regulation of adiposity. Angiotensinogen (AGT), the substrate from which ANG II is formed, was previously shown to be elevated in adipose tissue of obese (ob/ob and db/db) mice and regulated by nutritional manipulation. It is unknown, however, whether overexpression of adipose AGT can be extended to other models of obesity and whether hormonal and/or nutritional factors directly regulate AGT expression in adipocytes. We investigated these possibilities by analyzing AGT mRNA levels in adipose tissue of obese Zucker rats, viable yellow (Avy) mice, and humans and by treating 3T3-L1 adipocytes with insulin, glucose, and a beta-adrenergic agonist. We demonstrate that AGT mRNA is decreased by approximately 50 and 80%, respectively, in adipose tissue of obese vs. lean Zucker rats and Avy mice. We also report that AGT is expressed at variable levels in human adipose tissue. Finally, we show that AGT mRNA is upregulated by insulin and downregulated by beta-adrenergic stimulation in adipocytes.
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PMID:Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control. 924 55

We present a new hypothesis to explain the development of salt-dependent hypertension in humans. We propose that hypertension has two phases: an early phase in which elevations in blood pressure (BP) are mainly episodic and are mediated by a hyperactive sympathetic nervous or renin-angiotensin system, and a second phase in which BP is persistently elevated and that is primarily mediated by an impaired ability of the kidney to excrete salt (NaCl). We propose that the transition from the first phase to the second occurs as a consequence of catecholamine-induced elevations in BP that preferentially damage regions of the kidney (juxtamedullary and medullary regions) that do not autoregulate well to changes in renal perfusion pressure. The catecholamine response is associated with both an increase in peritubular capillary pressure and a reduction in peritubular capillary plasma flow, resulting in injury to the peritubular capillaries with ischemia to the tubules and interstitium. The local injury triggers the release or activation (angiotensin II, adenosine, renal sympathetic nerves) or inhibition (nitric oxide, prostaglandins, dopamine) of vasoactive mediators that further augment ischemia and result in abnormal tubuloglomerular feedback and enhanced NaCl reabsorption. The peritubular capillary injury with rarefaction simultaneously blunts the pressure natriuresis mechanism. The combined effect of enhanced tubuloglomerular feedback and impaired pressure natriuresis results in a defect in NaCl excretion which, on the exposure to salt, results in the development of persistent hypertension. Evidence is provided to suggest that this may be the major mechanism for the development of salt-dependent hypertension, and particularly for the hypertension associated with blacks, aging and obesity. Thus, essential hypertension may be a type of acquired tubulointerstitial renal disease.
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PMID:Hypothesis: the role of acquired tubulointerstitial disease in the pathogenesis of salt-dependent hypertension. 935 Jun 40

There has been increasing interest in the question of whether microalbuminuria can be used in the risk stratification of patients with essential hypertension. A cluster of cardiovascular and/or renal risk factors may be associated with microalbuminuria in hypertension. Despite this, prospective data about the potential role of microalbuminuria as a prognostic marker of cardiovascular and/or renal risk have been sparse and inconclusive until now. Blood pressure values have been considered the most important determinant of microalbuminuria in essential hypertension; however, hyperinsulinaemia--a metabolic component-was noted to be present in conjunction with high blood pressure. Furthermore, 2 other factors may be also related to microalbuminuria: salt sensitivity and renal structural changes (nephrosclerosis). We are now aware that the clinical and physiological implications of abnormal urinary albumin excretion (UAE) are much broader than anticipated, possibly involving haemodynamic, metabolic and vascular components overlapping several clinical syndromes. Achievement of short term UAE reduction with antihypertensive treatment depends on structural abnormalities established in the glomerulus, the extent of blood pressure reduction and the antihypertensive drug class used. In terms of UAE reduction, better results are obtained with ACE inhibitors or angiotensin II antagonists such as losartan and valsartan, than with other antihypertensive classes, although their true impact in preserving renal function needs to be assessed. The capacity of new calcium antagonists, such as amlodipine, lacidipine or mibefradil, to reduce UAE also needs to be assessed further. Thus, microalbuminuria may be seen as an integrated marker of risk and should be assessed in recently diagnosed patients with essential hypertension. In microalbuminuric patients, the target should be to decrease blood pressure < 135/85 mm Hg, reduce salt intake to around 100 mmol/day and prescribe a low-calorie diet if obesity is present. ACE inhibitors or angiotensin II antagonists have more potential benefits than the other classes of antihypertensive drugs in reducing UAE. Finally, a yearly assessment of microalbuminuria is recommended during treatment, to monitor the impact of therapy.
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PMID:Treatment of patients with essential hypertension and microalbuminuria. 942 93


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