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Biomedical subjects

A M Sharma

Publications and source records attributed to A M Sharma.

At least 19 recordsLinked to original sources
PubMed2001

[Treatment of hypertension in obesity].

BACKGROUND: Hypertension and obesity are common medical conditions independently associated with increased cardiovascular risk. Many large epidemiological studies have demonstrated associations between body mass index and blood pressure, and there is evidence to suggest, that obesity is a causal factor in the development of hypertension in obese subjects. Weight Reduction and maintenance is an essential first step in the treatment of obesity-associated hypertension. Weight reduction may be achieved by behavior modification, diet, and exercise or by the use of anti-obesity medication. However, the long-term outcomes of weight management programs for obesity are generally poor, and most hypertensive patients will require antihypertensive drug therapy. PATHOPHYSIOLOGY: Obese hypertensive patients often have metabolic abnormalities known to be exacerbated by commonly used antihypertensive agents but also obesity per se is often associated with endorgan damage including left ventricular hypertrophy, glomerular hyperfiltration and microalbuminuria, congestive heart failure or sudden cardiac death. Furthermore they have revealed volume expansion, increased cardiac output, and lower total peripheral resistance than lean patients. Hypertension in obese patients appears to be related to both increased sympathetic nervous system activity and activation of the renin-angiotensin system. Where antihypertensive therapy is necessary, the aim should be to use agents based on the hemodynamic and metabolic background and that have benefits beyond blood pressure lowering and improve the conditions most commonly linked with obesity-associated hypertension, such as hyperlipidaemia, Type II diabetes, left ventricular hypertrophy, coronary artery disease, or congestive heart failure. PHARMACOTHERAPY: Based on their favorable metabolic profiles, it would appear that ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, moxonidine and alpha-blockers can lower blood pressure without worsening the metabolic abnormalities, that is just one aspect of the problem. Yet, most guidelines fail to provide specific advice on the pharmacological management of hypertension in obese patients. This may be due to the fact that there are currently no studies that have addressed the efficacy of specific antihypertensive agents in reducing mortality in obese-hypertensive patients. This paper reviews the theoretical reasons for the differential use of the major classes of antihypertensive agents in the pharmacological management of obesity-related hypertension and also considers the potential role of anti-obesity agents.

Antihypertensive Agents↗
PubMed2001

The renin-angiotensin system and natriuretic peptides in obesity-associated hypertension.

Excessive accumulation of adipose tissue is associated with profound alterations in the cardiovascular system. including an increase in systemic blood pressure. It now appears clear that a central feature of obesity-associated hypertension is related to changes in sodium handling that may result from abnormalities in sympathetic nervous system activity, the renin-angiotensin-aldosterone system, natriuretic peptides, and kidney function. In this paper we review the role of these factors in the development of obesity-associated hypertension, thereby focusing on the potential role of adipose tissue in these alterations.

Adipose Tissue↗
PubMed2001

New developments in mechanisms of obesity-induced hypertension: role of adipose tissue.

Hypertension develops in almost 60% of obese individuals. Apart from the recent observation of obesity-associated structural changes in kidney structure that may lead to enhanced tubular sodium reabsorbtion, reports of paracrine and hormonal factors derived from adipose tissue have prompted speculations about the role of adipose tissue in the pathophysiology of obesity-induced hypertension. We summarize recent data on leptin's sympathoexcitatory actions, the possible influence of adipose tissue on atrial natriuretic peptide levels, and the formation of vasoactive substances, such as angiotensin II and nonesterified fatty acids, by adipocytes. The mechanisms discussed herein may contribute to the typical findings in obesity-induced hypertension, including volume expansion, sodium retention, enhanced sympathetic nervous system activity, increased activity of the systemic renin-angiotensin system, low atrial natriuretic peptide levels, and disturbed glucose and insulin metabolism. Together, these data strengthen the hypothesis that adipose tissue is potentially a major regulator of cardiovascular-renal function.

Adipose Tissue↗
PubMed2001

Metabolic and hemodynamic response of adipose tissue to angiotensin II.

OBJECTIVE: Recent studies have revealed the presence of a local renin-angiotensin system in adipose tissue. To examine the possible role of this system in adipose tissue, we performed microdialysis studies on the effect of angiotensin II (Ang II) on blood flow and metabolism in abdominal subcutaneous adipose tissue (aSAT) and femoral subcutaneous adipose tissue (fSAT) in young healthy men. RESEARCH METHODS AND PROCEDURES: Using the microdialysis technique, two different protocols were run perfusion with Ringer's solution + 50 mM ethanol with the subsequent addition of 125, 250, and 500 microg/liter Ang II (n = 8) and Ringers's solution + 50 mM ethanol with the subsequent addition of isoproterenol (1 microM) alone and in combination with 500 microg/liter Ang II (n = 6). Dialysate concentrations of ethanol, glycerol, glucose, and lactate were measured for estimating blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively. RESULTS: Perfusion with Ang II resulted in a dose-dependent decrease in blood flow (fSAT > aSAT), lipolysis (fSAT > aSAT), and glucose uptake (fSAT = aSAT). Isoproterenol increased blood flow and lipolysis at both sites and those effects could be returned to baseline values by the addition of Ang II in aSAT but not fSAT. DISCUSSION: In conclusion, our data indicate that in addition to its well-known vasoconstricting effect, Ang II inhibits lipolysis in adipose tissue, whereby femoral fat depots seem to be more sensitive to this effect than abdominal depots.

Adipose Tissue↗
PubMed2001

Tumor necrosis factor-alpha--308 G/A polymorphism in obese Caucasians.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism in the 5'-flanking region of the TNF-alpha gene (G-308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and influences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population. SUBJECTS AND METHODS: We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Ernährung Geschwister)- Study for the TNF-alpha-G-308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels. RESULTS: The frequency of the -308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (GG, n=118; GA, n=53; AA, n=5). There was a significant difference in allele frequencies of the polymorphism by BMI quartiles (I,<27.3 kg/m2; II, 27.3-31.9 kg/m2; III, 31.9-36.5 kg/m2; IV,>36.5 kg/m2, in each quartile n=44) with -308A allele carriers having a higher BMI than G allele carriers (P=0.013). Despite previous smaller studies that have related insulin resistance to the G-308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism. CONCLUSION: Our findings support the hypothesis that the G-308A polymophism of the TNF-alpha gene is associated with BMI. The G-308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians.

Alleles↗
PubMed2001

Extraction of total RNA from adipocytes.

RNA isolation from adipocytes presents with several technical problems and yields unacceptable results when following standard protocols. Here, we will describe additional steps and modifications necessary for the use of different RNA isolation protocols in terms of RNA yield, RNA quality and preparation time. Using five times the recommended quantity of lysis buffer, incubating the lysate at 37 degrees C, repeatedly passing the lysate through a cannula, and centrifugation to remove the lipid layer are essential additional steps when working with adipocytes. With these modifications, isolation of total RNA resulted in an average yield of 12-30 microg total RNA from 2 x 10(6) cells. Preparation times were similar for all but the CsCl gradient method. The purest RNA was obtained by spin-column purification, whereas acid phenol-chloroform methods yielded the highest amounts of total RNA. CsCl gradient ultracentrifugation is suggested for situations where DNase I digestion is impractical.

Adipocytes↗
PubMed2001

Salt-sensitivity and other predictors of stress-related cardiovascular reactivity in healthy young males.

Individuals whose mean arterial blood pressure is depending on oral salt intake are considered salt-sensitive and are at risk of developing essential hypertension. This study investigates the role of salt-sensitivity with respect to systolic blood pressure reactions under standardized mental stress. Forty-three healthy young males, previously characterized as salt-sensitive (n=16) or salt-resistant (n=27) by a dietary regimen, were subjected to multimodal physiological measurement during a computerized stress test and underwent comprehensive psychometrical testing. The most important predictors for systolic blood pressure reactions to stress were the degree of salt-sensitivity, body mass index and psychological characteristics like anxiety. The highest correlations with the degree of salt-sensitivity were found for the parameters age, systolic blood pressure reaction under stress, high frequency band of heart rate variability and two psychological variables. The concept of salt-sensitivity is a novel biological component that might contribute to reactivity research in subjects at high risk for essential hypertension.

Adult↗
PubMed2001

Choice of drug treatment for obesity-related hypertension: where is the evidence?

Hypertension and obesity are common medical conditions independently associated with increased cardiovascular risk. Many large epidemiological studies have demonstrated associations between body mass index and blood pressure, and there is evidence to suggest that obesity is a causal factor in the development of hypertension in obese individuals. Consequently, all hypertension management guidelines consider weight reduction as a first step in the management of increased blood pressure in obese individuals. Weight reduction may be achieved by behaviour modification, diet and exercise, or by the use of anti-obesity medications. However, the long-term outcomes of weight management programmes for obesity are generally poor, and most hypertensive patients will require antihypertensive drug treatment. Some classes of antihypertensive agents may have potentially unwanted effects on some of the metabolic and haemodynamic abnormalities that link obesity and hypertension, yet most hypertension guidelines fail to provide specific advice on the pharmacological management of obese patients. This may be because there are currently no studies examining the efficacy of specific antihypertensive agents in reducing mortality in obese hypertensive patients. This paper reviews the theoretical reasons for the differential use of the major classes of antihypertensive agents in the pharmacological management of obesity-related hypertension and also considers the potential role of anti-obesity agents.

Antihypertensive Agents↗
PubMed2001

Hypothesis: Beta-adrenergic receptor blockers and weight gain: A systematic analysis.

One of the arguments put forward against the primary use of beta-blockers has been concern about adverse metabolic effects, such as unfavorable effects on lipids or insulin sensitivity. Another less-appreciated potential drawback is their propensity to cause weight gain in some patients. In 8 evaluable prospective randomized controlled trials that lasted >/=6 months, body weight was higher in the beta-blocker than in the control group at the end of the study. The median difference in body weight was 1.2 kg (range -0.4 to 3.5 kg). A regression analysis suggested that beta-blockers were associated with an initial weight gain during the first few months. Thereafter, no further weight gain compared with controls was apparent. There was no relationship between demographic characteristics and changes in body weight. Based on these observations, the first-line use of beta-blockers in obese hypertensive patients should be reviewed. Obesity management in overweight hypertensive patients may be more difficult in the face of beta-blocker treatment.

Adrenergic beta-Antagonists↗
PubMed2001

Expression analysis using oligonucleotide microarrays in mice lacking bradykinin type 2 receptors.

We recently conducted detailed cardiovascular and blood pressure-related phenotypic studies of mice lacking the bradykinin-B(2) receptor and were unable to identify a phenotype despite insensitivity to infused bradykinin. We therefore used oligonucleotide microarray analysis of some 12 000 genes and expressed sequence tags to identify molecular mechanisms that might be involved in compensating for the lack of a functional B(2) receptor in the kidneys of the mice. We identified 2 gene families that may have an impact on cardiovascular regulation and the bradykinin pathway. A water transport channel in the kidney, AQP4, was downregulated in the mice, whereas other members of the gene family did not show differences in expression levels. In addition, a number of serine proteases were upregulated in B(2) receptor-deficient mice. These genes are all located within a gene cluster on mouse chromosome 7. The findings were verified by an independent method. We suggest that microarray analysis has usefulness in elucidating otherwise unappreciated compensatory signaling pathways.

Animals↗