Long-term octreotide treatment prevents vascular hyporeactivity in portal-hypertensive rats.
Chronically portal-hypertensive rats show in vitro vascular hyporeactivity in large part mediated by the endothelium-derived vasodilator nitric oxide. We tested whether long-term octreotide treatment (15 micrograms/kg subcutaneously in 5% D/W, 8-hourly) corrects the in vitro vascular hyporeactivity. Increases in perfusion pressures (delta mm Hg) to potassium chloride (30-300 mmol/L) of in vitro perfused superior mesenteric arterial vascular beds of partial portal vein-ligated (PVL) rats were significantly (P < .05) higher in octreotide (n = 9) compared with placebo (n = 10, 5% D/W) treated animals. Octreotide significantly (P < .05) increased mean arterial pressure compared with placebo, the values being 129 +/- 3 and 117 +/- 4 mm Hg, respectively. Furthermore, a significant (P < .001) correlation was observed between in vitro vascular reactivity and mean arterial pressure. Incubation of separate vascular beds (n = 7 for both PVL and sham-operated rats) with octreotide (10(-6) mol/L) did not enhance pressure responses to 125 mmol/L potassium chloride, and failed to increase perfusion pressures in preconstricted vessel preparations (n = 6), excluding a direct inhibitory effect on NO. In summary, long-term octreotide treatment prevents in vitro vascular hyporeactivity in prehepatic portal-hypertensive rats, and octreotide does not exert its action through direct effects on endothelium-derived NO.
Sieber
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Hepatic Hemodynamic Lab, VAMC West Haven, CT 06516, USA.
Lee
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Groszmann
R J
RJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006975:Hypertension, Portal / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D011189:Potassium Chloride; D001120:Arginine; D019001:Nitric Oxide Synthase; D015282:Octreotide