Comparison of the effects of intravenous and intrasplenic infusions of glucagon on cardiac output and its distribution in the rat

In order to determine whether or not glucagon released from the pancreas might have local vascular effects, the actions upon regional haemodynamics in the anaesthetised rat of two doses of glucagon (2 and 10 micrograms kg-1 min-1) infused intrasplenically (and thus into the portal vein) were compared with those of a single dose (2 micrograms kg-1 min-1) infused i.v. Infusion of glucagon i.v. produced a significantly increased heart rate (by 6%) and cardiac output (by 23%) in the experimental animals compared to those receiving saline by the same route. Total peripheral resistance fell by 24%. A greater proportion of the cardiac output passed to the coronary and renal vascular beds and blood flow was increased in the spleen, testes, pectoral skeletal muscle, stomach and small intestine as well as the heart and kidneys. The lower dose infused intrasplenically had no significant effect on cardiac output or total peripheral resistance but significantly increased the proportion of cardiac output passing both to the stomach and the small intestine such that the percentage of cardiac output flowing through the portal vein increased from 19.1 +/- 1.1% to 23.8 +/- 1.7%. Intrasplenic infusion of 10 micrograms kg-1 min-1 significantly increased cardiac output (by 29%) but reduced total peripheral resistance by 37%. Greater fractions of the cardiac output were received by the spleen, small intestine and epididymides. Blood flow was increased in these organs and the skin, kidneys, stomach, large intestine and the mesentery. It is concluded that pharmacologically effective amounts of glucagon only passed into the systemic circulation with the higher dose infused intrasplenically.