A new approach to NMR that allows non-purified urine samples to be analysed, has provided an answer to biochemical puzzle that has vexed scientists since the 1960s. The discovery of a candidate hormone that controls the flushing out of sodium from our bodies could help explain ion regulation and may lead to a new approach to treating high blood pressure.

Treating high blood pressure, or hypertension, often relies on lowering sodium levels in the blood. But, medications that interfere with ion transport and excretion all have serious side effects because they also reduce potassium levels. However, a drug that could modulate or even mimic the natural sodium control hormone, might allow blood pressure to be controlled effectively with minimal side effects. Frank Schroeder and colleagues at Cornell University have taken a new approach that has allowed them to identify a hormone in human urine - a xanthurenic acid derivative - that apparently controls the rate of sodium excretion and so could influence blood pressure.

Until this discovery, researchers were aware that aldosterone activates the kidney to reabsorb sodium and excrete potassium. The logical conclusion from that earlier discovery is that a second hormone must exist to stimulate the kidney to carry out the counter process: excretion of sodium and reabsorbtion of potassium. Finding such a compound in urine proved impossible until now because it is such a complex mixture of hundreds of different chemicals. Attempts to isolate the active hormone for testing was also impossible as it apparently breaks down during traditional chemical analysis.

Schroeder and colleagues began to look for a new approach in 2003 with backing from Naturon Pharmaceutical Corp. They turned to ¹H NMR and (¹H,¹H) dqf COSY NMR spectroscopy of enriched active fractions. The technique revealed three new compounds present in urine, which were tested for hormonal activity. Two of the compounds, both derivatives of a common metabolite xanthurenic-acid, raised sodium levels in vivo but maintained potassium at a constant level.

The newly discovered hormone is unlike aldosterone, which is steroidal, but resembles amino acid-derived neurotransmitters, such as dopamine and serotonin. He suspects the hormone may have several roles in the body. "We now want to know what other functions these compounds have and whether they directly influence blood pressure," says Schroeder.

"At this point, it is difficult to speculate about what other biological processes might be influenced by the newly identified compounds, and the next step will be to find the receptor(s) that the xanthurenic acid derivatives bind to," Schroeder told SpectroscopyNOW, "From our analyses, it appears that the two xanthurenic acid derivatives represent the actual signaling molecules - the activity is very well-defined and the compounds are of high specific potency. Furthermore, a closely related metabolite, xanthurenic acid itself, is not active."

Related links:

• Proc Natl Acad Sci, 2007, 104, 17873-17878
• Schroeder Page

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.