Researchers' discovery may lead to hypertension treatment
November 1st, 2007
Frank Schroeder inserts a natural product sample into a nuclear magnetic resonance spectrometer in the Department of Chemistry and Chemical Biology. NMR spectroscopy has evolved into the most important tool for identifying new biologically active compounds. Credit: Jason Koski
For more than 40 years, researchers have suspected there must be a natural hormone that could safely flush sodium out of the body and could be harnessed to develop more effective and safer treatments for high blood pressure, or hypertension. Currently, drugs that lower sodium levels all have serious side effects because they also reduce potassium levels.
Researchers at Cornell and the Boyce Thompson Institute for Plant Research (BTI) have used a new technique and identified a hormone from human urine -- a xanthurenic-acid derivative -- that seems able to do the job. The discovery opens the door to developing novel medications to control sodium levels and treat hypertension.
Frank Schroeder, an assistant scientist at BTI and co-author of the paper, which appeared in a recent issue of Proceedings of the National Academy of Sciences, developed a new technique for analyzing complex mixtures of small molecules, making it possible to finally identify the hormone.
Prior to the discovery, researchers knew that a human steroid called aldosterone activates the kidney to reabsorb sodium and excrete potassium, which led them to suspect that there must be another hormone that would trigger the kidney to do the opposite: excrete sodium and reabsorb potassium. Many had tried to find such a hormone in human urine, but urine contains a mix of hundreds of molecules, and the correct one could not be isolated, probably because the suspected hormone breaks down easily during traditional chemical analysis.
Most researchers had given up searching for this "holy grail" of kidney hormones, until, in 2003, a private company, Naturon Corp., contacted Schroeder, then a research associate at Cornell and Harvard Medical School.
To do the job, Schroeder developed an approach based on nuclear magnetic resonance (NMR) spectroscopy of partially purified urine. Traditionally, NMR spectroscopy, arguably the most powerful tool chemists use to determine the structures of unknown compounds, has only been used for the analysis of purified compounds. Schroeder's approach allows NMR to identify compounds without isolating them, for example in a complex mixture such as partially fractionated urine. The technique revealed three completely new compounds, each of which was subsequently synthesized and injected into rats. The rats' urine was then monitored.
Two of the identified compounds, both derivatives of a common metabolite xanthurenic-acid, raised sodium levels in the rat's urine but kept potassium levels constant. Schroeder said that while aldosterone (which does the opposite) is a steroid hormone, this newly discovered molecule is structurally more similar to such amino acid-derived neurotransmitters as dopamine and serotonin and, therefore, may also play other roles in the body.
"Now, we want to know what other functions these compounds have and whether they directly influence blood pressure," said Schroeder.
Source: Cornell University
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Volume 24 %u2022 Number 5 %u2022 June 2001 Medically Supervised Water-only Fasting in the Treatment of Hypertension
Alan Goldhamer, DC,a Douglas Lisle, PhD,b Banoo Parpia, PhD,c Scott V. Anderson, MD,d
and T. Colin Campbell, PhDe
INTRODUCTION
Hypertension-related diseases are the most common causes
of morbidity and mortality among industrially
High blood pressure (also known as hypertension) is the leading contributing cause of morbidity and mortality in industrialized societies, and is the leading reason for visits to doctors and for the use of prescription medication. It is diagnosed when a patient%u2019s pressures exceed 140/90 mm Hg. The human and financial costs of this condition are staggering.
In 1984, doctors at the TrueNorth Health Center began to investigate the use of fasting in the treatment of this devastating condition. Our study involved 174 high blood pressure patients, all of whom were admitted to the Center for treatment involving water-only fasting.
The results of the study were astonishing. Every patient experienced blood pressure reductions sufficient to eliminate the need for medication, and over ninety percent of patients achieved completely normal blood pressure. A stunning reduction of over 60 points in systolic (upper) blood pressure was noted in those patients with highly elevated pressures (known as Stage III Hypertension), where systolic pressures are greater than 180 mm Hg. These results represent the largest effect size ever shown in lowering blood pressure, and they are estimated to be five times the effect expected from medications alone.
With assistance from our colleagues at Cornell University, our study, %u201CMedically Supervised Water-only Fasting in the Treatment of Hypertension%u201D was completed and accepted for publication by the peer-reviewed and indexed Journal of Manipulative and Physiological Therapeutics. It appeared in the June, 2001 issue of JMPT.
A second study, also conducted at the Center, was recently accepted for publication in the Journal of Alternative and Complementary Medicine. In this investigation, we evaluated the effect of water-only fasting on 64 patients admitted with so-called %u201Cborderline%u201D hypertension. These are individuals who have systolic blood pressures between 120 and 140 mm Hg.
Patients with blood pressures in this range are often led to believe that their blood pressures are %u201Cnormal.%u201D For example, a patient with a systolic blood pressure of 138/88 would be considered %u201Cnormal%u201D by conventional medical standards, despite the fact that they are five times more likely to die from a heart attack or stroke than an individual who has a systolic blood pressure of 110 mm Hg. Sixty-eight percent of all deaths attributed to the effects of high blood pressure occur in individuals whose systolic blood pressure is in this range.
The patients in our second study had a mean reduction in systolic blood pressure of 20 mm Hg. The average patient in the study, beginning with a systolic blood pressure of nearly 130 mm Hg, ended his stay with systolic blood pressure of just below 109 mm Hg. This represents a very substantial improvement in health. As just stated, he is now five times less likely to die from a heart attack or stroke than he was before.