Angiotensin II-mediated pressor effect of rat joining peptide.
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.
Yoshida
M
M
Department of Biochemistry and Specialized Center of Research in Hypertension, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Hamakubo
T
T
Inagami
T
T
D000804:Angiotensin II / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D007275:Injections, Intravenous; D019808:Losartan; D008297:Male; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013565:Sympatholytics / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D010446:Peptide Fragments; D010455:Peptides; D013565:Sympatholytics; D013777:Tetrazoles; C078895:joining peptide, pro-opiomelanocortin; D000804:Angiotensin II; D011333:Pro-Opiomelanocortin; D002216:Captopril; D019808:Losartan