(Hypertension. 1995;26:213-220.)
© 1995 American Heart Association, Inc.
Articles |
Chromogranin A in Human Hypertension
Influence of Heredity
From the Departments of Medicine and Family and Preventive Medicine, University of California, San Diego; the Department of Veterans Affairs Medical Center, San Diego; and Charles R. Drew University of Medicine and Science, Los Angeles, Calif.
Correspondence to Daniel T. O'Connor, MD, Division of Nephrology-Hypertension (9111H), University of California, San Diego, 3350 La Jolla Village Dr, San Diego, CA 92161. E-mail doconnor@ucsd.edu.
Abstract Multiple heritable traits are associated with
essential (genetic) hypertension in humans. Because chromogranin A is
increased in both human and rodent genetic hypertension, we examined
the influence of heredity and blood pressure on chromogranin A in
humans. In estimates derived from among- and within-pair variance in
monozygotic versus dizygotic twins, plasma chromogranin A displayed
significant (F15,18=2.93, P=.016) genetic
variance (
2g), and its broad-sense
heritability was high (h2B=0.983).
Plasma chromogranin A was increased in essential hypertension
(99.9±6.7 versus 62.8±4.7 ng/mL, P<.001) but was
influenced little by genetic risk for (family history of) hypertension
(in normotensive or hypertensive subjects), by race, or by several
antihypertensive therapies (angiotensin-converting enzyme
inhibitor, diuretic, or ß-adrenergic
antagonist). In normotensive subjects at genetic risk for
essential hypertension, neither basal nor sympathoadrenal stress-evoked
chromogranin A differed from values found in subjects not at risk. In
established essential hypertension, plasma chromogranin A responses to
adrenal medullary (insulin-evoked hypoglycemia) or sympathetic neuronal
(dynamic exercise) activation were exaggerated, whereas responses to
sympathoadrenal suppression (ganglionic blockade) were diminished,
suggesting increased vesicular stores of chromogranin A and an
adrenergic origin of the augmented chromogranin A expression in this
disorder. We conclude that plasma chromogranin A displays substantial
heritability and is increased in established essential hypertension.
Its elevation in established hypertension is associated with evidence
of increased vesicular stores of the protein and with adrenergic
hyperactivity but is influenced little by customary antihypertensive
therapies. However, the chromogranin A elevation is not evident early
in the course of genetic hypertension.
Key Words: chromogranins • hypertension, essential • adrenal medulla • genetics
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