AJP - Regulatory, Integrative and Comparative Physiology, Vol 266, Issue 3 802-R808, Copyright © 1994 by American Physiological Society
Angiotensin II-mediated pressor effect of rat joining peptide
M. Yoshida, T. Hamakubo and T. Inagami
Department of Biochemistry and Specialized Center of Research in Hypertension, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
In an attempt to determine the mechanism of pressor action of centrally
administered rat joining peptide (rJP), a pro-opiomelanocortin
(POMC)-derived peptide, we investigated its action on the angiotensin and
adrenergic system in the brain stem. In conscious spontaneously
hypertensive rats with chronic cannulas in the cisterna magna and abdominal
aorta, the pressor effect of synthetic rJP in the cisterna magna was
markedly inhibited by pretreatment with losartan, an antagonist of
angiotensin (ANG) II receptor specific for its AT1 subtype, and also by the
nonspecific antagonist [Sar1,Ile8]ANG II but not by AT2-specific PD-123319.
Pretreatment with captopril did not alter the pressor response. Adrenergic
receptor antagonists, yohimbine and propranolol, did not change the pressor
response. The intracisternal joining peptide administration (10 and 30
nmol) increased the concentration of immunoreactive ANG II in cerebrospinal
fluid 2.4- and 5.7-fold, respectively. These results indicate that the
pressor response to rJP is mediated by the release of central ANG II and
AT1 receptor. This study details a biological response to rJP, the only
POMC-derived peptide whose action has not been identified previously.
