Histamine may protect against damage to heart and kidneys

New research on mice shows histamine in cardiorenal syndrome protects the heart and kidneys.

Mice research finds histamine can protect against harm to the heart and kidneys.
Mice research finds histamine can protect against harm to the heart and kidneys.

Heart failure, or congestive heart failure, affects approximately 5.7 million people in the US. The condition has not got a cure yet.

Chronic kidney disease also affects a large percentage of the U.S. population, affecting 14 percent, and causing death in 47,000 cases.

In a phenomenon they call the cardiorenal syndrome, doctors closely link the two conditions— a paragliding term for several disorders that affect both the heart and the kidneys.

An acute or chronic dysfunction in one organ can trigger acute or chronic dysfunction in the other in cardiorenal syndrome, and an increasing number of studies are trying to understand why.

An acute or chronic dysfunction in one organ may cause acute or chronic dysfunction in the other in cardiorenal syndrome, and an growing number of studies are trying to understand why.

For example, mounting evidence suggests that “heart-to-neck physiological contact is needed to maintain cardiovascular homeostasis,” and researchers have used this lens to explain how chronic kidney disease increases the risk of heart failure.

Other studies investigated the role of the sympathetic nervous system in cardiorenal syndrome, oxidative stress, inflammation, and the so-called renin-angiotensin (RAS).

Most of these studies have looked at cardiac and renal function separately, the authors of the latest research say, since the number of animal models that can reproduce dysfunction effectively in both systems at once is inadequate.

Their work aims to fill the research void by providing a suitable model for animals. The senior and corresponding author of the new paper is Akiyoshi Fukamizu, a professor at the University of Tsukuba, Japan.

Using a mouse model, Prof. Fukamizu and his team have discovered histamine’s unexpected protective effect in cardiorenal syndrome. They also published their findings in the National Academy of Sciences journal Proceedings.

A mouse model of cardiorenal syndrome

The authors demonstrate in their paper that treating animals with Ang II — a vasoconstrictive hormone in RAS — has shown to affect blood pressure, as well as homeostasis of electrolytes and blood volumes.

Ang II can play a crucial role in the damage that occurs in cardiorenal syndrome, some experts have suggested.

Prof. Fukamizu and colleagues used the Ang II hormone for this new study to induce hypertension in mice, partial surgical removal of the kidneys to induce inflammation in the kidneys, and salt to cause fluid retention.

These treatments together recreated cardiorenic syndrome features in the rodents.

Histamine and heart, kidney dysfunction

The researchers found that the levels of histamine in blood plasma were high in this animal model they produced in this particular way.

They also found that this high histamine concentration had a protective effect on the heart and kidneys, rather than a negative one.

To further test what was an interesting finding, Prof. Fukamizu and team proceeded to apply multiple substances that blocked various histamine receptors, until they found that blocking the H3 histamine receptor exacerbated cardiorenal damage.

Consequently, heart contractility was weaker, creatinine clearance — or the capacity of the kidney to remove creatinine from the blood through urine— was also reduced, and the heart in those mice had increased in size.

Furthermore, the researchers gave the mice an H3 histamine agonist — that is, a substance that mimics the action of the natural histamine compound — and found it to be protected from cardiorrhea.

“Histamine is an important factor in various inflammatory processes, and its inhibition usually leads to better control of the disease,” states Prof. Fukamizu.

“In a mouse model of cardiorenal syndrome, we found elevated levels of histamine which were remarkably protective against further damage in these mice.”

– Akiyoshi Fukamizu

“We found that targeting the H3 histamine receptor with an agonist, immethridine, in our mouse model could substantially relieve some of the cardiorenal damage components,” the researcher continues to write.

“In addition, immethridine therapy has resulted in protective changes in gene expression that have affected multiple genes associated with inflammation in these mice.”

Researchers hope that their results will help bring new treatments for human cardiovascular dysfunction.

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