FROM SCIENCE TRANSLATIONAL MEDICINE
The hormone vasopressin, well known for its antidiuretic effects, also appears to stimulate proliferation and differentiation of red blood cell (RBC) precursors, results of a series of preclinical investigations suggest.
Treating anemic mice with an arginine vasopressin (AVP) receptor agonist increased hematocrit and reticulocyte counts significantly, compared with controls, according to the results published in Science Translational Medicine (2017 Nov 29;9:eaao1632).
“AVP appears to jump-start peripheral blood cell replenishment until EPO [erythropoietin] can take over,” wrote Balázs Mayer, PhD , of the National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH), Bethesda, Md., and his coauthors.
That finding could have implications for the development of new treatments designed to stimulate RBC production after bleeding, chemotherapy, or drug toxicity, according to the investigators.
“Currently, EPO is the only agent that is used clinically to stimulate erythropoiesis, but there are patients who do not respond to EPO or who cannot take the drug because it stimulates tumor growth,” the investigators wrote. “AVP appears to be an EPO-independent, fast-acting agent that increases RBC numbers after anemia.”
Dr. Mayer and his colleagues initially asked whether AVP might play a role in RBC production after observing that patients with central diabetes insipidus (CDI), who lack the antidiuretic hormone, are frequently anemic. A review of patient records from an NIH database revealed that 60% of CDI patients were anemic despite treatment with desmopressin.
They subsequently found that all three AVP receptor subtypes are expressed in human and mouse hematopoietic stem and progenitor cells. In particular, the AVPR1B subtype appeared to play the most important role in regulating erythropoiesis.
Accordingly, they tested the ability of both AVP and a AVPR1B-specific agonist to stimulate production of RBCs in mice that had anemia induced by bleeding or irradiation. They found significant improvements in both hematocrit and reticulocyte numbers as early as 2 days after treatment started.
Subsequent experiments were designed to determine whether the effect of AVP on RBC production was caused by EPO release. In fact, the effects of AVP occurred “long before an effect of EPO was observed,” investigators wrote.
The research was supported by the NIH. Some of the study authors are listed as inventors on a patent application held by the U.S. Department of Health and Human Services covering methods for modulating erythropoiesis with arginine vasopressin receptor 1b molecules.
