Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic effects of isosorbide dinitrate in rats with cirrhosis.
The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 micrograms/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414 +/- 25 vs 290 +/- 26 dyn.s/cm-5 per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98 +/- 6 vs 79 +/- 7 mmHg), systemic vascular resistance (318 +/- 30 vs 207 +/- 10 dyn.s/cm-5 per 100 g), portal pressure (14.0 +/- 1.0 vs 11.3 +/- 0.9 mmHg) and portal territory vascular resistance (1362 +/- 163 vs 1031 +/- 182 dyn.s/cm5 per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone.
Kirstetter
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P
Laboratoire d'Hémodynamique Splanchnique, INSERM U-24, Hôpital Beaujon, Clichy, France.
Pilette
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C
Moreau
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R
Cailmail
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S
Safka
V
V
Soupison
T
T
Lebrec
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D
D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005730:Ganglionic Blockers / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D011168:Portal System / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000759:Adjuvants, Anesthesia; D005730:Ganglionic Blockers; D014665:Vasodilator Agents; D018738:Hexamethonium; D010424:Pentobarbital; D007548:Isosorbide Dinitrate