Vasopressin gene transcripts in mineralocorticoid hypertension: an in situ study.
OBJECTIVE
To test the hypothesis that enhanced expression of the vasopressin gene accompanies the development of deoxycorticosterone acetate (DOCA)-salt hypertension in the rat and to compare the response with those observed during chronic hypernatremia.


METHODS
Transcript levels were determined by measurement of vasopressin messenger RNA (mRNA) in the supraoptic nucleus and paraventricular nucleus by in situ hybridization, autoradiography and image analysis. Plasma, urinary and pituitary vasopressin were determined by radioimmunoassay.


METHODS
High-resolution localization and measurement of specific mRNA in the supraoptic and paraventricular nuclei before and during development of DOCA-salt hypertension were compared with corresponding results in both age-matched controls and normal rats that drank hypertonic saline.


RESULTS
Vasopressin mRNA levels were increased in the paraventricular nucleus during the established and chronic stages of DOCA-salt hypertension, but were unchanged in the supraoptic nucleus. Urinary excretion of vasopressin was increased in the prehypertensive, established and chronic phases of DOCA-salt hypertension, whereas plasma vasopressin levels were increased only in the chronic phase. Pituitary vasopressin levels were unchanged. In comparative studies, vasopressin mRNA levels in both the supraoptic and paraventricular nuclei and plasma vasopressin were significantly increased in normal rats drinking 2% saline.


CONCLUSIONS
Whereas hypernatremic rats showed markedly elevated vasopressin transcripts in the supraoptic and paraventricular nuclei, DOCA-salt hypertension is associated with increased vasopressin mRNA in the paraventricular but not the supraoptic nucleus. The response in the paraventricular nucleus may explain part of the increased peripheral vasopressin levels and suggests that this nucleus makes a critical contribution to the pathogenesis of DOCA-salt hypertension.
Ashen
M D
MD
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205.
Hartman
R D
RD
Barraclough
C A
CA
Petersen
S L
SL
Hamlyn
J M
JM
D000818:Animals; D003900:Desoxycorticosterone; D015870:Gene Expression; D006955:Hypernatremia / Q000235:genetics* / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008955:Models, Cardiovascular; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry*; D010902:Pituitary Gland / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000737:chemistry*; D014158:Transcription, Genetic; D014667:Vasopressins / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D014667:Vasopressins; D003900:Desoxycorticosterone