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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data in support of the hypothesis that insulin-mediated sympathetic stimulation contributes to the hypertension that occurs in association with obesity are presented. The relation between insulin and the sympathetic nervous system derives from the effect of diet on sympathetic activity. Fasting suppresses but overfeeding stimulates the sympathetic nervous system. Insulin-mediated glucose metabolism within central neurons sensitive to insulin and glucose appears to be one important signal in this relation between diet and sympathetic activity. In the obese, hyperinsulinemia and hypertension track together in epidemiological studies. Evidence from a human population-based study (the Normative Aging Study) indicates that the abdominal form of obesity is associated with both hyperinsulinemia and increased urinary norepinephrine excretion. Elevations in urinary norepinephrine excretion, moreover, were highest in those with the highest fasting levels of insulin and glucose. These observations are consistent with the hypothesis that insulin-mediated sympathetic stimulation is a mechanism recruited in the obese to increase metabolic rate and restore energy balance; concomitant increases in sympathetic stimulation of the heart, vasculature, and kidney result in hypertension, which, according to this formulation, is an unfortunate by-product of the cardiovascular response to a metabolic adaptation.
Hypertension 1992 Jan
PMID:Hyperinsulinemia: possible role in obesity-induced hypertension. 173 Apr 56

We performed euglycemic clamp studies with labeled glucose to measure insulin's effect on hepatic glucose output (HGO) and peripheral glucose clearance in eight conscious mobile spontaneously hypertensive rats (SHR) and eleven normotensive Wistar-Kyoto (WKY) rats age 9-10 wk. Systolic blood pressure was elevated in the SHR (P less than 0.001), whereas means of 12-h-fasted plasma insulin (P greater than 0.4), glucose (P greater than 0.07), HGO (P greater than 0.25), and glucose clearance (P greater than 0.2) did not differ significantly between groups. Infusions of human insulin into SHR and WKY rats (1 and 1.5 mU.min-1.kg-1, respectively) during concomitant somatostatin administration reestablished basal insulinemia in both groups. Neither HGO (P greater than 0.15) nor glucose clearance (P greater than 0.3) differed significantly between SHR and WKY rats under those conditions. Somatostatin plus higher-dose insulin infusions (4 mU.min-1.kg-1 in SHR and 3 or 6 mU.min-1.kg-1 in WKY rats) resulted in physiological hyperinsulinemia in all rats. Insulin sensitivity, calculated as the increase in glucose clearance effected by an increase in circulating insulin during higher-dose insulin infusions, did not differ significantly between SHR and WKY groups (P greater than 0.3). HGO was completely suppressed in SHR and WKY rats during the higher-dose insulin infusions. Our data indicate that hypertension is present in SHR at an age when insulin-mediated glucose disposal is not different from age-matched WKY rats. These findings do not support a role for peripheral insulin resistance in the genesis of hypertension in SHR.
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PMID:Hypertension without peripheral insulin resistance in spontaneously hypertensive rats. 173 45

Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors. 173 2

Insulin resistance (IR) appears to be an important risk factor of both hypertension and atherosclerosis. Moreover, it is present also in obesity, dyslipoproteinaemia and non-insulin dependent diabetes. IR could be found in untreated hypertension and even in normotensive children of hypertensive parents. It alters carbohydrate, lipid and protein metabolism and participates directly in the development of hypertension. The diagnosis of IR is possible by simple determination of insulin and glyceamia during glucose tolerance test. The differential diagnosis is obligatory because IR is not specific just for hypertension. Treatment, with the exception of nonpharmacological measures, is unsatisfactory. However, results of newest research are highly promising.
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PMID:Essential hypertension and insulin resistance. 174 23

Patients with hypertension have been shown to be resistant to insulin-stimulated glucose uptake and to be both hyperinsulinemic and hypertriglyceridemic compared with matched normotensive control groups. These abnormalities are present before the institution of antihypertensive therapy and do not necessarily improve when blood pressure is effectively lowered. Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and high blood pressure can be produced in fructose-fed Sprague-Dawley rats, but the development of these changes is inhibited by exercise training or somatostatin infusion. Furthermore, insulin-stimulated glucose uptake is lower in spontaneously hypertensive rats (SHRs) than Wistar-Kyoto rats, and this is associated with higher plasma triglyceride concentrations and blood pressure. In addition, a defect in insulin-stimulated glucose uptake can be shown in adipocytes isolated from SHRs, and the greater the degree of in vitro insulin resistance, the higher the plasma insulin concentration and blood pressure. These data strongly support the view that abnormalities of insulin and lipid metabolism are associated with high blood pressure in both patients and rodent models of experimental hypertension. In the latter context, endogenous hyperinsulinemia and hypertriglyceridemia are risk factors for coronary heart disease. The fact that antihypertensive treatment has not focused on correcting these metabolic abnormalities may explain why it has been difficult to show that lowering blood pressure decreases the risk of coronary heart disease. It can be argued that abnormalities of carbohydrate and lipoprotein metabolism play a role in both the etiology of hypertension and the clinical course of hypertensive patients.
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PMID:Relationship between insulin resistance and hypertension. 174 55

Hypertension, a condition characterized by narrowing of the arteriolar lumen, is related in part to vasoconstriction and in part to vascular hypertrophy. Complex and interlocking mechanisms involving the autonomic nervous system and both circulating and local vasoconstrictor and vasodilator hormones contribute to this narrowing. Endothelin, 5-HT (serotonin), the kinins and ouabain may all participate by altering sodium, potassium and calcium fluxes in vascular smooth muscle cells. Recently the concept of insulin resistance as a mechanism of hypertension has emerged. Insulin may be a vascular growth factor as well as a local hormone facilitating a rise in intracellular sodium concentration. The observation that ACE inhibitors lower BP when plasma renin and angiotensin levels are low has led to an increased interest in local non-circulating renin-angiotensin systems. These systems probably influence arteriolar tone as well as vascular hypertrophy, and their inhibition leads to reduction in BP and some reversal of arteriolar thickening. Thus the ACE inhibitors represent a logical and effective method of treating hypertension and their use is likely to increase in the next few years.
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PMID:The mechanisms of hypertension and the role of ACE inhibitors. 179 16

Antihypertensive Therapy has been ineffective in reducing the incidence of coronary artery disease. It has been suggested that the metabolic and biochemical alterations induced by some antihypertensive drugs may be responsible for their failure to reduce cardiovascular mortality in patients with hypertension. Hypertension is only one of multiple coronary risk factors associated to insulin resistance. This cluster of risk factors is call "The Syndrome of Insulin Resistance" by some and "Syndrome X" by Reaven and others. Is important to know this information when pharmacological antihypertensive therapy is contemplated.
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PMID:Hypertension: a new perspective in therapy and metabolic effect. Part I. 180 74

Hypertension and diabetes are common diseases in Westernized civilizations, and in the United States, the frequency of both diseases is increasing as the society ages. Factors contributing to the high prevalence and increasing frequency of these diseases include obesity, hyperinsulinemia and insulin resistance, genetic factors, and abnormal cellular handling of calcium and other cations. Obesity is a strong early predictor for the development of hypertension as a person progresses from childhood into adult life. Important factors contributing to obesity-related hypertension likely include enhanced sympathetic nervous system activity and insulin resistance and hyperinsulinemia. Recent evidence has also shown that many nonobese adults with untreated hypertension have insulin resistance and hyperinsulinemia. This observation strongly suggests that the disease called "hypertension" is characterized by fundamental metabolic abnormalities as well as by hemodynamic abnormalities. Recent observations have shown that impaired cellular responses to insulin are associated with increased vascular smooth muscle contraction. Insulin appears to attenuate the vascular response to both receptor-mediated and voltage-mediated calcium-induced contractions. Thus, insulin resistance, and the resultant reduction in the normal attenuating effect of insulin on vascular smooth muscle responses, appear to be associated with abnormal vascular smooth muscle handling of calcium and with exaggerated vascular contraction.
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PMID:Insulin resistance, carbohydrate metabolism, and hypertension. 183 73

Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. 186 24

Recent data from this laboratory indicate that insulin resistant obese Zucker rats exhibit hypertension associated with exaggerated in vitro vascular reactivity to phenylephrine, serotonin, and KCl, and we have found insulin to attenuate vascular reactivity responses to these agonists. Accordingly, in the present study we evaluated the possibility that exaggerated vascular reactivity responses in obese Zucker rats may result from insulin resistance and a consequent failure of insulin to attenuate vasoactive responses. Thoracic aortae were isolated from male 16 week old lean and obese Zucker rats, and replicate helical strips from each animal were suspended in a muscle bath under a resting tension of 1.4 g in the presence or absence of insulin (0.1 mU/mL) for 1 h. The insulin was then washed out, and vascular reactivity responses to phenylephrine were determined. The obese rats exhibited greater reactivity to phenylephrine (ED50:1.10 +/- 90 X 10(-8) v 7.57 +/- 0.88 X 10(-10) mol/L in lean and obese rats, respectively, P less than .025). Insulin caused a significant attenuation of the contractile response in both the lean and obese aortae. However, lean rats exhibited a markedly greater attenuation than the obese rats (46.0 +/- 17.0 v 17.8 +/- 7.5% attenuation in the lean and obese rats, respectively, P less than .01). These data suggest that increased vascular reactivity responses in obese Zucker rats may result from their insulin resistant state and, consequently, a diminished ability of insulin to attenuate vasoconstrictor responses.
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PMID:Insulin attenuation of vasoconstrictor responses to phenylephrine in Zucker lean and obese rats. 187 6


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