Effects of continued NO inhibition on portal hypertensive syndrome after portal vein stenosis in rat.
The present study investigated whether chronic nitric oxide (NO) inhibition prevents the hyperdynamic circulatory syndrome that appears in rats after partial portal vein ligation (PPVL). N omega-nitro-L-arginine methyl ester (L-NAME; 30 micrograms.kg-1.min-1, n = 17), a NO biosynthesis inhibitor, or vehicle (n = 17) was infused continuously from PPVL through subcutaneously osmotic pumps. Studies were performed, in ketamine-anesthetized Sprague-Dawley rats, in one-half of the animals at 4 days and in the remaining one-half at 8 days from PPVL. At 4 days, PPVL rats treated with L-NAME had higher mean arterial pressure (MAP), systemic vascular resistance (SVR), and splanchnic arteriolar resistance (SAR) and lower cardiac output and portal venous inflow (PVI) than PPVL rats treated with vehicle (P < 0.05). Similarly, at 8 days PPVL rats treated with L-NAME had higher MAP and SVR and lower cardiac output (P < 0.05) than PPVL rats treated with vehicle. In contrast, PVI and SAR were similar. At 4 days plasma volume and mesenteric-systemic shunting were lower, although nonsignificantly, in PPVL rats treated with L-NAME. This trend completely disappeared at 8 days. L-NAME did not change portal pressure at either 4 or 8 days. After 4 days of continuous treatment with L-NAME, nonportal hypertensive control rats had a significantly higher MAP, lower cardiac index and PVI, and higher SVR and SAR than nonportal hypertensive rats treated with vehicle. Contrary to PPVL rats, these effects were maintained after 8 days of treatment. The present study shows that NO contributes to the systemic disturbances of portal hypertension. However, NO inhibition delayed but did not prevent the splanchnic vasodilation that appears after PPVL, suggesting that other factors could also be involved.
García-Pagán
J C
JC
Hepatic Hemodynamics Laboratory, Hospital Clínic i Provincial, Barcelona, Spain.
Fernández
M
M
Bernadich
C
C
Pizcueta
P
P
Piqué
J M
JM
Bosch
J
J
Rodés
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005934:Glucagon / Q000097:blood; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects
D009569:Nitric Oxide; D005934:Glucagon; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester