ANGIOTENSIN II-MEDIATED PRESSER EFFECT OF RAT JOINING PEPTIDE

In an attempt to determine the mechanism of presser action of centrall y administered rat joining peptide (rJP), a pro-opiomelanocortin (POMC )-derived peptide, we investigated its action on the angiotensin and a drenergic system in the brain stem. In conscious spontaneously hyperte nsive rats with chronic cannulas in the cisterna magna and abdominal a orta, the presser effect of synthetic rJP in the cisterna magna was ma rkedly inhibited by pretreatment with losartan, an antagonist of angio tensin (ANG) II receptor specific for its AT(1) subtype, and also by t he nonspecific antagonist [Sar(1),Ile(8)]ANG II but not by AT(2)-speci fic PD-123319. Pretreatment with captopril did not alter the presser r esponse. Adrenergic receptor antagonists, yohimbine and propranolol, d id not change the presser response. The intracisternal joining peptide administration (10 and 30 nmol) increased the concentration of immuno reactive 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 detail s a biological response to rJP, the only POMC-derived peptide whose ac tion has not been identified previously.