Heart peptide goes to the head.

Heart Peptide Goes to the Head

As part of the brain's security system,the blood-brain barrier is very selective about what passes through its gates. Yet there's a glitch in this arrangement of rigid checks and balances: It is particularly susceptible to fluid buildup in head injuries and certain diseases. The central nervous system's handling of this dangerous edema has been little understood. But recent research indicates that it may be a case of the heart controlling at least a part of the brain.

James A. Nathanson and Luca Steardoof Harvard Medical School and Massachusetts General Hospital in Boston report in the Jan. 23 SCIENCE that brain barrier tissues carry receptors for a cardiac peptide -- and that this peptide can affect the rate of spinal fluid production. Some researchers believe the peptide could have treatment implications for edema within the next decade.

Secreted by the heart, the hormone -- calledatrial natriuretic peptide (ANP) or atrial natriuretic factor -- can act as a diuretic, influencing fluid movement. It was discovered in the heart less than a decade ago; subsequent studies of its role in sodium and water regulation nominated the peptide as a possible treatment for hypertension (SN: 1/17/87, p.42). Although its receptors have been found elsewhere in the body, most notably in the kidney, the boston study is the first to describe ANP action at the crucial blood-brain interface.

The brain's barrier system essentiallyhas two parts: the blood-brain barrier, made up of endothelial cells lining the brain's blood vessels (see adjacent story), and the blood-cerebrospinal fluid (CSF) barrier, made up of the epithelial cells of the choroid plexuses. Found deep inside the brain the choroid plexuses are network structures that produce CSF, which in turn "cushions" the central nervous system. Nathanson and Steardo focused their search for ANP receptors on the choroid epithelium from rabbits.

Biochemical assays showed that theisolated cells were "very heavily enriched" with receptors for the peptide, according to Nathanson. He told SCIENCE NEWS that the ANP mechanism at the brain barriers is significant for reasons that go beyond its possible role in regulating fluid volume. "It may be the first clear example of a membrane-associated receptor that activates guanylate cyclase directly," he says.

That particular enzyme is responsiblefor production of guanosine 3',5 -monophosphate (cGMP), found throughout the body and possibly important in mediating hormonal action.

Because the cells so rich in ANP receptorsalso produce CSF, the researchers used catheterized rabbits to examine the effect of the peptide on CSF production. Injection of ANP caused an average 35 percent drop in CSF secretion in the rabbits. Parallel studies of ANP injected into the eye showed a drop in intraocular pressure.

Why does the body have a fluid-regulatingcardiac peptide with far-flung receptor sites, one that decreases CSF output and increases cGMP production? The final answers await further research, but the significance of ANP research is not disputed, says a review article in the Jan. 16 JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (JAMA). Clinical trials in the United States and elsewhere show infusion of the peptide makes blood pressure quickly drop, which has attracted the interest of pharmaceutical companies since one in five adults suffers from high blood pressures.

But ANP treatment of fluid-retentionconditions like that found in congestive heart failure may precede treatment for hypertension, according to the JAMA article. Aram V. Chobanian, director of the Cardiovascular Institute at Boston University School of Medicine, was quoted in JAMA as asaying that ANP might be used to treat edema within five to 10 years. But he cautions that it may be much longer before this naturally occurring hormone is used as a blood pressure drug.

It is too early, Nathanson says, to knowwhether ANP will be useful in treating cerebral edema, a serious threat in strokes, cerebral hemorrhage, infections, tumors and head trauma. Nonetheless, the choroid epithelial cell system should provide an accessible model for further ANP study.