Effects of cholecystokinin (CCK-33) and its fragments, C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4), on the circulatory system of diabetic rats.
The effect of cholecystokinin (CCK-33) and its fragments, C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4), on arterial blood pressure and on the function of the isolated rat heart was studied in three groups of animals: normal (C group), rats with streptozotocin-induced diabetes of one month's duration (DM group) and with diabetes treated with insulin (DMI group). CCK-33 (5.0, 10.0 and 20.0 U/kg iv) raised dose-dependently systolic and diastolic arterial blood pressure but did not change the heart rate in the group of normal rats. CCK-33 administered in doses of 1.0, 2.0, 5.0 U/0.1 ml) increased the amplitude of the isolated heart contraction and reduced heart rate but had no effect on coronary outflow in this group. In the diabetic rats, CCK-33 in dose 20.0 U/kg iv reduced the arterial blood pressure and had no effect on heart rate in vivo. CCK-33 increased the cardiac contraction amplitude and lowered heart rate of the isolated heart from the diabetic rats. In the group of insulin-treated diabetic rats, CCK-33 did not change the blood pressure, increased the heart rate in vivo. This peptide increased the cardiac contraction amplitude, no lowering of the heart rate of the isolated heart was noted. CCK-8 and CCK-4 had no effect on arterial blood pressure and the function of the isolated heart in any of the groups of animals studied. The results indicate that shortening of CCK-33 to CCK-8 and CCK-4 eliminates the circulatory effect of this peptide and that in diabetes CCK-33 produces circulatory effects opposite to those observed in normal animals. Insulin partially normalizes the action of CCK-33 on the circulation in diabetes.
Fiedorowicz
R J
RJ
Chair and Department of Pharmacology, Bialystok Medical School, Poland.
Wiśniewski
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology*; D013758:Tetragastrin / Q000494:pharmacology*
D007328:Insulin; D010446:Peptide Fragments; D013758:Tetragastrin; D002766:Cholecystokinin; D012844:Sincalide