Opiate and alpha receptor antagonists block the pressor responses of conscious rats given intravenous dynorphin.
Conscious, unrestrained rats were used to determine the hemodynamic (blood pressure and heart rate) responses following intravenous (IV) injection of dynorphin A(1-13) and the possible receptor mechanisms mediating those changes. Male Sprague-Dawley rats (300 g) were given IV bolus injections (via femoral venous catheter) of 6.0 to 600 nmoles/kg of dynorphin A(1-13), 8.0 nmoles/kg of norepinephrine HCl (NE), 14.3 pmoles/kg of angiotensin II or a vehicle control solution. Blood pressure (BP) and heart rate (HR) were monitored via femoral arterial catheter (into abdominal aorta) over 90 sec postpeptide or -amine administration before and 10 min after IV injection of 4.2 mumoles/kg of naloxone HCl (opiate antagonist), yohimbine HCl (alpha 2 receptor antagonist) or prazosin HCl (alpha 1 receptor antagonist). Dynorphin A(1-13) caused a transient but dose-related rise in mean arterial pressure (MAP) whereas mean pulse pressures (MPP) and mean heart rates (MHR) concomitantly fell, from preinjection control values in a dose-dependent fashion. Pretreatment with naloxone blocked the pressor response of only a subsequent injection with 20 nmoles/kg but not 60 nmoles/kg of dynorphin A or NE (8.0 nmoles/kg). Pretreatment with yohimbine suppressed the marked pressor responses of subsequent NE or Dyn A (60 nmoles/kg) administration whereas prazosin antagonized the rise in MAP of only the lower doses of dynorphin as well as NE. The suppression of the pressor responses of dynorphin by opiate or alpha receptor antagonists were not caused by tachyphylaxis for repeated injections of 6.0 or 60 nmoles/kg of dynorphin caused the same rise in MAP.(ABSTRACT TRUNCATED AT 250 WORDS)
Thornhill
J A
JA
Department of Physiology, University of Saskatchewan, Saskatoon, Canada.
Gregor
L
L
Saunders
W S
WS
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011674:Pulse / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D012016:Reference Values; D015016:Yohimbine / Q000494:pharmacology*
D010446:Peptide Fragments; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D000804:Angiotensin II; D015016:Yohimbine; D009270:Naloxone; C026843:dynorphin (1-13); D004399:Dynorphins; D009638:Norepinephrine