Hypertension Clinical Trial
we propose that bromocriptine may be an alternative treatment of primary aldosteronism, both APA and BAH.
Primary aldosteronism (PA), a common curable disease of hypertension, is characterized by
inappropriate production of aldosterone, which is at least partially autonomous of the
renin-angiotensin system. A recent clinical study reported that patients with PA experience
a higher sate of a higher rate of cardiovascular events than those with essential
hypertension(Corry and Tuck 2003; Milliez, Girerd et al. 2005). The prevalence of metabolic
syndrome was higher in primary aldosteronism than in essential hypertension was also
reported (Fallo, Veglio et al. 2006). The wide applying of the plasma aldosterone/plasma
rennin activity (ARR) as a screening test among hypertensive patients have reported a much
higher prevalence of this disease, up to 12% of hypertensive patients. In the past decade,
an increase in diagnosis rate of PA has been observed in National Taiwan University
Hospital, with an average of 15-20 newly diagnosis cases every year.
Idiopathic bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenoma (APA) are
the leading causes of primary aldosteronism. Unilateral adrenalectomy is the reasonable
therapeutic option of APA and aldosterone antagonists usually brings about well blood
pressure (BP) control in BAH. Not every APA patient would accept operation because of other
medical conditions, or the cure rate of hypertension in APA after adrenalectomy is 50-70% in
most studies. For patients with BAH, aldosterone antagonists are the first choice of
treatment, however, intolerance to high dose of these medications is not uncommon. To our
best knowledge, there is no alternative treatment for these patients.
Dopaminergic regulation of aldosterone secretion has been well demonstrated in normal
subjects as well as patients with PA. We have shown that D2 receptor can down-regulate the
transcription of aldosterone synthase (CYP11B2) via a specific PKC isoform and probably
intracellular calcium level. Furthermore, there is a reciprocal change of the mRNA of D2
receptor and CYP11B2 in APA. D2 receptor has also been demonstrated in other neuroendocrine
tumors, eg., pheochromocytoma, prolactinoma, GH-secreting adenoma ect. [Camacho & Mazzone
1999] Administration of D2 agonist, bromocriptin (BMC), is a standard treatment of
prolactinoma, either for pre-operative reduction of the tumors or for non-surgical patients
[Chattopadhyay et al., 2005]. Reduction or shrinkage of prolactinoma has been observed in
patients treated with BMC [Biswas et al., 2005]. Anti-proliferative effect and apoptosis of
BMC have been demonstrated in several cell lines [Wasko et al., 2004]. Recently, we also
demonstrated that BMC, in addition to decrease aldosterone secretion and expression of
CYP11B2, could inhibit cell proliferation of H295 cells, an adrenocortical carcinoma cell
line, with a down-regulation of ERK. In this context, we propose that BMC may be an
alternative treatment of PA, both APA and BAH.
;
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