Mechanism of action of the anti-shock effect of CCK-8: influence of CCK antagonists and of sympatholytic drugs.
In an experimental model of haemorrhagic shock that causes 100% mortality in rats within 30 min, the intravenous bolus injection (20 micrograms/kg) of sulfated cholecystokinin octapeptide (CCK-8) induces a prompt and sustained rise in blood pressure and pulse amplitude, all treated animals still surviving at the end of the experiment (2 h). This effect of CCK-8 is completely blocked by reserpine (5 mg/kg i.p.), significantly antagonized by prazosin (0.1 mg/kg i.v.) and yohimbine (1 mg/kg i.v.), and unaffected by practolol (15 mg/kg i.v.) and proglumide (0.2 mg/kg i.v.); it is completely antagonized by the intravenous (0.01-0.05 mg/kg), but not by the intracerebroventricular (0.002 mg/kg) injection of the 'peripheral' CCK antagonist, L-364,718. The present data indicate that the cardiovascular effects of CCK-8 in haemorrhagic shock involve peripheral CCK receptors, and require the functional integrity of the sympathetic nervous system.
Guarini
S
S
Institute of Pharmacology, University of Modena, Italy.
Vergoni
A V
AV
Bertolini
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D013565:Sympatholytics / Q000494:pharmacology
D011949:Receptors, Cholecystokinin; D013565:Sympatholytics; D012844:Sincalide