Catecholamine secretory vesicles. Augmented chromogranins and amines in secondary hypertension.
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 beta-hydroxylase by Northern blot. Immunoreactive adrenal chromogranin A was 3.3-fold higher (p < 0.01) in clipped rat adrenals. Adrenal catecholamine concentrations and phenylethanolamine-N-methyltransferase activity were also higher in clipped rats. Adrenal dopamine beta-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 beta-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.
Department of Medicine, University of California, San Diego 92161.
M A
MA
Takiyyuddin
L
L
De Nicola
F B
FB
Gabbai
T Q
TQ
Dinh
B
B
Kennedy
M G
MG
Ziegler
E L
EL
Sabban
R J
RJ
Parmer
D T
DT
O'Connor
D000313:Adrenal Medulla / Q000378:metabolism; D000588:Amines / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002395:Catecholamines / Q000378:metabolism*; D002864:Chromogranins / Q000235:genetics / Q000378:metabolism*; D003250:Constriction; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D006801:Humans; D006978:Hypertension, Renovascular / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery
D000588:Amines; D002395:Catecholamines; D002864:Chromogranins; D012333:RNA, Messenger; D004299:Dopamine beta-Hydroxylase