Catecholamine secretory vesicles: Augmented chromogranins and amines in secondary hypertension

Abstract

Chromogranins A and B are major soluble proteins in chromaffin granules. Their adrenomedullary content is increased in the spontaneously (genetic) hypertensive rat. Is augmented catecholamine vesicular storage of the chromogranins a specific feature of genetic hypertension? To explore this question, we measured chromogranin A immunoreactivity, using a novel, synthetic peptide radioimmunoassay, in rat adrenal medullas 4-6 weeks after induction of the two-kidney, one clip Goldblatt model of renovascular hypertension and in unmanipulated control animals. We also measured messenger RNAs of chromogranins A and B and dopamine β-hydroxylase by Northern blot. Immunoreactive adrenal chromogranin A was 3.3-fold higher (p<0.01) in clipped rat adrenals. Adrenal catecholamine concen-trations and phenylethanolamine-N-methyltransferase activity were also higher in clipped rats. Adrenal dopamine β-hydroxylase activity (both membrane-bound and soluble forms) and corticosterone (glucocorticoid) concentration did not significantly differ between the groups. Adrenal medullary chromogranin A messenger RNA levels in clipped rats were 3.2-fold higher (p=0.029) than those in the control group, and chromogranin B messenger RNA levels were 4.6-fold higher (p=0.05). Dopamine β-hydroxylase messenger RNA levels were 2.9-fold higher (p=0.038). Thus, augmented synthesis and storage of adrenomedullary chromogranins A and B, catecholamines, and their biosynthetic enzymes appear to be characteristic of both acquired and genetic hypertension.