ANGIOTENSIN II-MEDIATED PRESSER EFFECT OF RAT JOINING PEPTIDE

In an attempt to determine the mechanism of presser 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 presser 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 AT(1) subtype, and also by the nonspecific antagonist [Sar(1),Ile(8)]ANG II but not by AT(2)-specific PD-123319. Pretreatment with captopril did not alter the presser response. Adrenergic receptor antagonists, yohimbine and propranolol, did not change the presser 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 presser response to rJP is mediated by the release of central ANG II and AT(1) receptor. This study details a biological response to rJP, the only POMC-derived peptide whose action has not been identified previously.