Active Ingredient in Chinese Herb Used to Reduce High Blood Pressure

Some 50 million Americans have hypertension, that is, blood pressure measuring above the normal range (less than 120/80 mmHg). If untreated, it can lead to heart attacks, strokes, or kidney disease. Lifestyle changes are the first-stage treatment for the disease, but if they fail, medications are prescribed.

Many patients with high blood pressure have sought relief from complementary and alternative medicine (CAM). In so doing, many have consumed danshen, a Chinese herb used in Oriental medicine that promotes blood flow and treats cardiovascular disease.

Tanshinone IIA is an active ingredient of danshen. Since tanshinone IIA is widely available, a team of researchers has used it to investigate if this active ingredient can reduce blood pressure. In a soon-to-be-released study, using an animal model, the scientists have found that tanshinone IIA does reduce blood pressure.

Summary of Methodology

To assess the effect of tanshinone IIA, the protocol consisted of several parts. The researchers applied the 2-kidney-1-clip protocol to induce renal hypertension in male golden Syrian hamsters. The animals were anesthetized and a retroperitoneal approach was used to place a silver clip to constrict the right renal artery. Sham-operated hamsters and mice underwent the same procedure, except for the placement of a clip.

Both sets of hamsters received 50 ¦Ìg of tanshinone IIA/100g of body weight once a day for two weeks. After the two-week treatment period, mean arterial blood pressure was measured in the right carotid artery. To examine the microvascular actions of tanshinone IIA researchers applied it topically to the hamsters¡¯ cheek pouch or mice cremaster muscles to achieve the final concentration of one ¦Ìg/ml or five ¦Ìg/ml. After the application of tanshinone IIA, the experiment was continued for an additional 60-minute period in order to measure arteriolar diameter and peri-arteriolar nitric oxide concentration.

Results

Tanshinone IIA was found to have significantly reduced blood pressure in the hamsters. The experimental constriction of the renal artery increased mean arterial pressure to 161.2¡À6.9 mmHg relative to 114.3¡À9.2 mmHg in age-matched hamsters. Treatment with 50 ¦Ìg tanshinone IIA/100g body for two weeks reduced the mean arterial pressure from 161.2¡À6.9 to 130.0¡À7.8 mmHg.

The research team also discovered that tanshinone IIA caused widening of the arterioles in the hamster cheek pouch microcirculation via enhanced expression of endothelial nitric oxide synthase. The topical application of tanshinone IIA at one ¦Ìg/ml and five ¦Ìg/ml caused significant dose-related vasodilation, indicated by the increased agent/control ratio of arteriolar diameters from 1.0 to 1.25¡À0.08 and 1.57¡À0.11, respectively, in the hamster cheek pouch. The increase in arteriolar diameter ratio was significant relative to the vehicle for each concentration as well as for comparison between the two concentrations of tanshinone IIA.

Conclusions

As a result of the findings the researchers concluded that tanshinone IIA: (1) significantly reduced blood pressure in hamsters, (2) enhanced the expression of endothelial nitric oxide synthase, (3) increased the production of nitric oxide and (4) induced blood pressure changes through vasodilation in hamster blood microvessels. While the mechanisms of how tanshinone IIA or danshen work in hypertension are not yet fully understood, these results contribute to the effort to bring complementary and alternative medicine and allopathic care closer together in the treatment of hypertensive patients.

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Article adapted by MD Only from original press release.
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Contact: Donna Krupa
American Physiological Society

Their study will soon be published in the American Journal of Physiology ¨C Heart and Circulatory Physiology (December 15, 2006), doi:10.1152/ajpheart.01027.2006, and is entitled Endothelial Nitric Oxide Synthase is a Molecular Vascular Target for the Chinese Herb Danshen in Hypertension. It was conducted by the team of David D. Kim, PhD, OMD; Fabiola A. S¨¢nchez, PhD; Ricardo G. Dur¨¢n, BS; Takehito Kanetaka, MD; and Walter N. Dur¨¢n, PhD, all of the Program in Vascular Biology, Department of Pharmacology and Physiology and Department of Surgery, UMDNJ-New Jersey Medical School, Newark, NJ.

JOURNAL PUBLICATION INFORMATION: American Journal of Physiology ¨C Heart and Circulatory Physiology Articles in Press, doi: 10.1152/ajpheart.01027.2006.

Physiology is the study of how molecules, cells, tissues and organs function to create health or disease. The American Physiological Society (APS) has been an integral part of this scientific discovery process since it was established in 1887.

Sports Participation Reduces Risk of Blood Clots up to 39%

According to a new study published in Journal of Thrombosis and Haemostasis, regular participation in sports reduces the risk of developing blood clots by 39 percent in women and 22 percent in men.

Researchers from Leiden University Medical Center in the Netherlands evaluated 7,860 people aged 18-70. Patients who had suffered their first blood clot in a leg vein or lung artery were compared with control subjects who had never experienced blood clots. 31 percent of the patients and 40 percent of the control group participated in sports on a regular basis.

Overall figures for both sexes showed that participating in sports at least once per week, regardless of the type of sport or its intensity, reduced the risk of developing a blood clot in a lung artery by 46 percent and a blood clot in a leg vein by 24 percent.

“Women were shown to be even more likely to reap the benefits of regular sporting activities than men,” says F.R. Rosendaal, co-author of the study. “When we excluded women who were pregnant or receiving oral contraceptive or hormone replacement therapy – all possible causes of blood clots – the risk for women was reduced by 55 percent.”

The authors note that, while strenuous activity is known to increase the risk of blood clot development in the elderly, regular exercise is also shown to greatly benefit the heart, and that the net effect of elderly sports participation may be positive.

The findings also show that people who did not participate in sports were more than four-times as likely to develop a blood clot if they were obese (with a body mass index of 30 or greater) than lean (with a body mass index of less than 25).

“When we looked at the results, we found that, overall, the mere fact that people took part in a sporting activity at least once a week was enough to lower their risk of blood clots,” say the authors.

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Article adapted by MD Only Weblog from original press release.
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Contact: Sean Wagner
http://www.blackwellpublishing.com

_________________________________________________________________
This study is published in Journal of Thrombosis and Haemostasis.

To view the abstract for this article, please http://www.blackwell-synergy.com/doi/abs/10.1111/j.1525-1438.2007.00928.x http://www.blackwell-synergy.com/doi/abs/10.1111/j.1524-4733.2007.00186.x http://www.blackwell-synergy.com/doi/abs/10.1111/j.1526-4637.2007.00312.x http://www.blackwell-synergy.com/">click here.

Journal of Thrombosis and Haemostasis publishes high quality, original research reports, state-of-the art reviews, invited commentaries and debates on timely topics, letters and announcements on thrombosis, bleeding disorders and vascular biology. It is produced monthly by Wiley-Blackwell on behalf of the International Society on Thrombosis and Haemostasis.

Brain hormone wires people to be obese or thin

Some brains may be wired to encourage fidgeting and other restless behaviors that consume calories and help control weight, according to new research published by The American Physiological Society.

The study found that the brains of rats bred to be lean are more sensitive to a chemical produced in the brain, orexin A, which stimulates appetite and spontaneous physical activity such as fidgeting and other unconscious movements. Compared to rats bred to be obese, the lean rats had a far greater expression of orexin receptors in the hypothalamus.

“The greater expression of orexin receptors suggests the lean rats’ brains were more sensitive to the orexin the brain produces,” said Catherine M. Kotz, the study’s senior researcher. “The results point to a biological basis for being a couch potato.”

This line of research suggests that frequent minor unconscious movements such as fidgeting and other behaviors associated with restlessness burn calories and help control weight, Kotz said. Further, it suggests a strategy to reduce weight gain and could lead to the development of a drug to stimulate minor activity.

The study “Elevated hypothalamic orexin signaling, sensitivity to orexin A and spontaneous physical activity in obesity resistant rats,” appears in the online edition of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology published by The American Physiological Society. The study was done by Jennifer A. Teske and Allen S. Levine of the University of Minnesota and the Minnesota Obesity Center, St. Paul; Michael Kuskowski, VA Medical Center, Minneapolis; James A. Levine, Mayo Clinic, Rochester, Minnesota; and Catherine M. Kotz, the VA Medical Center, University of Minnesota, and the Minnesota Obesity Center.

Study looks at obese versus lean rats

“Many people focus on diet, but it may be more feasible for some people to stand or move more throughout the day” as a way to control their weight, Kotz said. Contrary to common belief, metabolism rates don’t vary greatly from person to person and weight gain usually results from eating too much, burning too few calories, or both, she said.

The researchers drew their conclusions after performing a series of experiments with obesity-prone and obesity-resistant rats. The obesity-prone strain was developed for obesity research by breeding obese rats with other obese rats. The obesity-resistant rats were developed by breeding lean rats with lean rats, Kotz noted. The study also employed a control group of normal laboratory rats.

Each rat consumed the same number of calories each day. The researchers took baseline measurements of each rat’s activity using sensors to measure even minor movements, such as grooming and standing.

They found that the lean group moved significantly more during this baseline period than the obese group, Kotz said. This was true even though the rats were young and both groups weighed the same — eliminating the obesity itself as the cause of the decreased movement. After the baseline data gathering, the researchers moved to the experimental part of the study.

Lean rats have elevated expression of orexin receptors

“We knew from previous studies that orexin stimulated physical activity, and so we wanted to find out whether it enhances activity more in lean rats than in obese rats, Kotz explained. The researchers injected orexin into the lateral hypothalamus area of the brains of both groups and found that the lean rats became even more active, while the obese rats didn’t respond much at all. “Not only do the lean rats have a higher base activity rate but they respond more to orexin,” she said.

Orexin must bind to receptors in the brain to produce increased activity, so the researchers reasoned that the lean rats must have more orexin receptors. When they did a blind analysis of the brains of obese and lean rats of various ages, they found that the lean rats had double the gene expression level of orexin receptors compared to the obese rats, Kotz explained.

The greater gene expression of orexin receptors does not conclusively prove that there are more orexin receptors, but it is highly suggestive of that finding. Kotz and her fellow researchers are now looking to see if the lean rats have a greater number of orexin receptors in their brains.

Activity level important to weight control

Because the rats in this study ate the same amount of food, the researchers concluded that the weight gain of the obese rats comes more from expending too few calories than from consuming too many. Other studies have shown that disabling the orexin system of lean rats causes them to eat less and move less, which leads them to become obese, Kotz said. When the orexin system is working optimally, the increase in eating which orexin causes is believed to be offset by increased physical activity, she said.

It would be impossible to do a similar study of the brain in humans. But one of the researchers, James Levine, found in a previous study with humans that lean individuals move about two hours per day more than obese individuals. What does this mean for those who are overweight?

“If we can get obese individuals to a slightly higher level of activity, that would be very beneficial,” Kotz concluded.

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Article adapted by MD Only Weblog from original press release.
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Contact: Christine Guilfoy
American Physiological Society

Hormone links sleep, hunger and metabloism

While investigating how the hormone orexin might control sleep and hunger, researchers at UT Southwestern Medical Center have discovered, to their surprise, that it activates a protein, HIF-1, long known to stimulate cancerous tumor growth. 

The study, appearing today in the online version of the journal Genes and Development, is among the first to show how HIF-1 operates in healthy tissues rather than in tumors, said Dr. Thomas Kodadek, chief of translational research at UT Southwestern and senior author of the study. 

“HIF-1 is very big in the cancer community,” Dr. Kodadek said. “So we were intrigued to find this important and very basic mechanism that is unrelated to cancer.” 

Orexin was already known for its role in sleep and hunger. Researchers, including Dr. Masashi Yanagisawa, professor of molecular genetics at UT Southwestern, had found that lack of orexin causes the sleep disorder narcolepsy.  

“It’s really the most straightforward system relevant to the biology of sleep you can look at,” Dr. Kodadek said. “You lack orexin? You’ve got narcolepsy. End of story.” 

Dr. Kodadek’s project is part of an initiative funded by the National Heart, Lung and Blood Institute to develop technologies to understand and treat sleep disorders.  In the current study, the researchers used a massive gene-screening technique to identify genes that orexin either turned on or inhibited. 

Surprisingly, the activity of a component of HIF called HIF1-alpha was among the most highly activated of any gene in the study. And when orexin stimulated HIF1-alpha, it in turn increased the expression of a variety of genes dedicated to burning sugar to provide energy for the body. Studies in brain slices of mice with and without orexin receptors support their results. 

The findings help explain orexin’s link to the metabolic system, the researchers said. The body is known to step up its production of orexin when blood sugar gets low. The researchers hypothesized that when a body has low blood sugar and gets hungry, the increase in orexin activates HIF-1 production, revving up metabolism so the body gets the most energy out of the sugar on hand.  

This action of HIF-1 when stimulated by orexin is different than how it acts in tumors, Dr. Kodadek said. In tumors, HIF-1 changes cells’ metabolism so they can burn sugar for energy without oxygen. This method is inefficient, but allows cells to stay alive.  

Orexin, on the other hand, forces HIF-1 to switch cells to burn sugar using oxygen, which burns sugar faster but more efficiently. This strategy makes sense, they said, in terms of evolution.  

“You need to be active and energetic, especially when you’re hungry, so you can search for a meal,” said Dr. Devanjan Sikder, instructor of internal medicine and lead author of the study. 

“This orexin pathway we found is basically an overdrive function. Even though blood sugar levels are low, you’re not only awake, but you’re also energetic because of the action of HIF-1,” said Dr. Kodadek. “In retrospect, our findings make a lot of sense, but they were surprising at the time.”  

Not only was this orexin-HIF link unexpected, but it showed an entirely new way HIF-1 operates, Dr. Kodadek said. There have been a few recent studies on its function in healthy tissues, but none involving mechanisms related to sleep, he said. 

The study also illustrates a potential complication of anti-cancer therapies that target HIF-1, Dr. Kodadek said. These results reveal that anti-HIF-1 chemotherapy could interfere with this essential function.  

“If anything, our findings may be a cautionary tale about whether HIF-related mechanisms are going to be appropriate targets for chemotherapy,” Dr. Kodadek said.  

The researchers next plan to genetically engineer mice that lack HIF-1 in the brain in order to determine the effects on wakefulness and activity levels of the animals. They also plan to further study how orexin and oxygen levels interact to control energy metabolism in cells.

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Article adapted by MD Only Weblog from original press release.
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Contact: Aline McKenzie
UT Southwestern Medical Center

Reduce the risk of hypertension by 50 percent drinking skim milk

The American Journal of Clinical Nutrition is the peer-reviewed journal of international reference in the field of nutrition. In its latest issue, of November, it published an article which demonstrated that non-fat milk products can reduce the risk of hypertension by 50%, while nevertheless there is no appreciable connection between that disease and the consumption of whole milk.

The research was carried out by a team of researchers from the University of Navarra and Álvaro Alonso, currently a researcher in the School of Public Health at Harvard University who is the lead author of the article.

Research population of 6,000 persons.

This was a study which evaluated the relationship between the consumption of milk products and the risk of developing arterial hypertension.

They performed a research project that followed 6,000 people over the course of two years.

Those persons with an elevated consumption of skimmed milk and milk products showed a reduction of 50% in their risk of developing hypertension, compared with those with a low consumption or who did not consume these products. Nevertheless, no relationship was encountered between the consumption of whole milk products and the risk of hypertension.

These results can contribute to a clearer definition of dietary guidelines for the prevention of arterial hypertension. In particular, although data from prior studies indicated a possible preventative role of lactose products in the development of arterial hypertension, these results have been the first to demonstrate that this association exists in adults.

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Article adapted by MD Only Weblog from original press release.
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Contact: Garazi Andonegi
Elhuyar Fundazioa

Lack of sleep doubles children and adults risk of obesity

Research by Warwick Medical School at the University of Warwick has found that sleep deprivation is associated with an almost a two-fold increased risk of being obese for both children and adults.

Early results of a study by Professor Francesco Cappuccio of the University of Warwick’s Warwick Medical School were presented to the International AC21 Research Festival hosted this month by the University of Warwick.

The research reviewed current evidence in over 28,000 children and 15,000 adults. For both groups Professor Cappuccio found that shorter sleep duration is associated with almost a two-fold increased risk of being obese.

The research also suggests that those who sleep less have a greater increase in body mass index and waist circumference over time and a greater chance of becoming obese over time.

Professor Cappuccio says:

“The ‘epidemic’ of obesity is paralleled by a ’silent epidemic’ of reduced sleep duration with short sleep duration linked to increased risk of obesity both in adults and in children.These trends are detectable in adults as well as in children as young as 5 years.”

Professor Cappuccio points out that short sleep duration may lead to obesity through an increase of appetite via hormonal changes caused by the sleep deprivation. Lack of sleep produces Ghrelin which, among other effects, stimulates appetite and creates less leptin which, among other effects, suppresses appetite. However he says more research is needed to understand the mechanisms by which short sleep is linked to chronic conditions of affluent societies, such as obesity, diabetes and hypertension.

Francesco Branca, the Regional Adviser for nutrition and food security in the World Health organisation (WHO) Regional Office for Europe said:

“This is an interesting piece of research putting together different lifestyle aspects with food choices. We need more research on the obese environment – the integration between medical research and socio-political research is something we should be exploring more.”

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Article adapted by MD Only Weblog from original press release.
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Contact: Peter Dunn
University of Warwick

Are You Fueling Your Heart For Life or Death?

An age-related decline in heart function is a risk factor for heart disease in the elderly. While many factors contribute to a progressive age-related decline in heart function, alterations in the types of fuels the heart uses to produce energy also play important roles. Jason Dyck and his research team at the University of Alberta have been studying the types of fuels used by the heart in young and aged mice. The young healthy heart normally used a balance of fat and sugar to generate energy to allow the heart to beat and pump blood efficiently. However, as the heart ages the ability to use fat as an energy source deteriorates. This compromises heart function in the elderly. Interestingly, at a time when the heart is using less fat for energy, Dyck has shown that a protein that is responsible for transporting fat into the contractile cells of the heart actually increases. Based on this finding, Dyck proposed that the mismatch between fat uptake and fat use in the heart could lead to an accumulation of fat in the heart resulting in an age-related decrease in heart function.

Using a genetically engineered mouse that is deficient in a protein that is responsible for transporting fat into the cells of the heart, Dyck studied these mice as they aged. These genetically altered mice have no choice but to mainly use sugar as a fuel source because they lack the protein that allows them to use fat as a primary fuel source. In an exciting new finding, Dyck showed that old genetically modified mice did not accumulate fat in their hearts, as did ordinary mice. In addition, Dyck and his team showed that these old genetically altered mice out-performed ordinary old mice on a treadmill test, were completely protected from age-related decline in heart function, and in many ways their hearts looked and performed like hearts from a young mouse. His findings suggest that the protein responsible for transporting fat into the contractile cells of the heart may be a candidate for drug inhibition and that this drug could protect the heart from aging.

This research holds great promise for human beings. Dyck hopes it will lead to the development of medications that inhibit the uptake of fatty acids into the heart and prevent and/or reverse the effects of aging on the heart muscle.

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Article adapted by MD Only Weblog from original press release.
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Contact: Kris Connor
University of Alberta

This study appears in the October 22 edition of Circulation.

Drinking coffee elevates plasma homocysteine raising risk of coronary heart disease

High plasma homocysteine concentration is associated with an increased risk of cardiovascular disease, and consumption of unfiltered and filtered coffee raises homocysteine levels. As yet, it is unclear which substances in brewed coffee are responsible for its homocysteine-raising properties. In an article published in this month’s American Journal of Clinical Nutrition, Verhoef et al. investigated the effects of caffeine alone and in brewed coffee on homocysteine concentrations in a group of healthy volunteers. Brewed coffee increased homocysteine levels within hours of consumption and seemed to have a particularly strong effect when taken after meals.

The 21 male and 27 female participants in the study, aged 19 to 65 years old, were all heavy coffee drinkers who consumed 6 or more cups of filtered or instant coffee daily. Thirty-one percent of the subjects were smokers, who are known to metabolize caffeine more rapidly than non-smokers. Three treatments, administered in random order for a period of 2 weeks each, consisted of either capsules containing 870mg of caffeine daily; 4 cups of strong filtered coffee that contained 870 mg of caffeine; or placebo capsules. Despite the fact that both treatments had a similar amount of caffeine, the average fasting homocysteine concentration rose by 11% after the subjects drank brewed coffee for 2 weeks, compared to a 5% increase after caffeine alone. The paper filter in the brewed coffee retained trace amounts of several substances that were suspected to be responsible for the rise in homocysteine concentrations, including chlorogenic acid (a polyphenolic compound) that is not removed by filtering.

Epidemiologic associatations between coffee consumption and CVD are conflicting; therefore, public health implications of the homocysteine-raising effects of caffeine and coffee will remain unclear until a causal relation between high homocysteine concentrations and CVD is proven.

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Article adapted by MD Only Weblog from original press release.
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Contact: Elizabeth Horowitz
American Journal of Clinical Nutrition

Verhoef, Petra et al. Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans. Am J Clin Nutr 2002;76:1244-8.

This information should not be construed as medical advice. If you have a medical concern, consult your doctor. To see the complete text of this article, please go to:

http://www.faseb.org/ajcn/Dec2002/13024.Verhoef.PDF