Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats.
The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 microgram.min-1.kg-1), isosorbide dinitrate (10 micrograms.min-1.kg-1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21 +/- 4% and portal pressure 17 +/- 3%. Isosorbide dinitrate decreased portal venous inflow 20 +/- 4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14 +/- 2%. Portal venous resistance rose 7.6 +/- 3% with isosorbide dinitrate alone, but decreased 18 +/- 4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22 +/- 4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
N
N
Hori
T
T
Okanoue
Y
Y
Sawa
Y
Y
Itoh
T
T
Mori
S
S
Takami
K
K
Kashima
D000704:Analysis of Variance; D000818:Animals; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000503:physiopathology; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000627:therapeutic use*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications*; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D017082:Portal Pressure / Q000187:drug effects; D011169:Portal Vein / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013853:Thioacetamide; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D013853:Thioacetamide; D007548:Isosorbide Dinitrate; D015282:Octreotide