Alpha-lactorphin lowers blood pressure measured by radiotelemetry in normotensive and spontaneously hypertensive rats.
Cardiovascular effects of subcutaneous administration of synthetic alpha-lactorphin, a tetrapeptide (Tyr-Gly-Leu-Phe) originally derived from milk alpha-lactalbumin, were studied in conscious spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY) with continuous radiotelemetric monitoring. Alpha-lactorphin dose-dependently lowered blood pressure (BP) without affecting heart rate in SHR and WKY. The lowest dose which reduced BP was 10 microg/kg, and the maximal reductions in systolic and diastolic BP (by 23+/-4 and 17+/-4 mm Hg, respectively) were observed at 100 microg/kg dose in SHR. No further reductions were obtained at a higher dose of 1 mg/kg. There were no significant differences in the BP responses to alpha-lactorphin between SHR and WKY. Naloxone (1 and 3 mg/kg s.c.), a specific opioid receptor antagonist, abolished the alpha-lactorphin-induced reduction in BP and reversed it into a pressor response, which provides evidence for an involvement of opioid receptors in the depressor action of the tetrapeptide.
Nurminen
M L
ML
Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland. marja-leena.nurminen@helsinki.fi
Sipola
M
M
Kaarto
H
H
Pihlanto-Leppälä
A
A
Piilola
K
K
Korpela
R
R
Tossavainen
O
O
Korhonen
H
H
Vapaatalo
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D011957:Receptors, Opioid; C102982:alpha-lactorphin; D009270:Naloxone; C065679:icatibant; D002216:Captopril; D001920:Bradykinin