Hyperkinetic circulation and decreased sensitivity to vasoconstrictors following portacaval shunt in the rat. Effects of chronic nitric oxide inhibition.
OBJECTIVE
This study aimed to investigate: (i) whether the hyperkinetic circulation that develops after portacaval shunt is associated with decreased vascular sensitivity to vasoconstrictors and (ii) the role of nitric oxide on its pathogenesis.


METHODS
Portacaval-shunted and sham-operated rats received long-term treatment with the nitric oxide inhibitor L-NAME (osmotic minipump) or its inactive enantiomer D-NAME. Measurements of arterial pressure, cardiac output and superior mesenteric artery blood flow (transit-time flow probe) were done 4 days later in baseline conditions and after increasing doses of methoxamine. Peripheral and superior mesenteric vascular resistance were calculated.


RESULTS
Portacaval shunted rats showed a significantly lower peripheral and superior mesenteric vascular resistance and a significant reduction in their response to incremental doses of methoxamine than sham-operated controls. Chronic nitric oxide inhibition attenuated the systemic but not the splanchnic vasodilatation and totally corrected the hyposensitivity to methoxamine of portacaval-shunted rats. However, they still had a significantly lower peripheral and superior mesenteric vascular resistance than sham-operated rats.


CONCLUSIONS
This study shows that the splanchnic and systemic hyporesponsiveness to methoxamine observed in portacaval-shunted rats could be explained by an excess of nitric oxide. However, other factors may be involved in maintaining splanchnic and systemic vasodilatation despite NO-inhibition.
Bandi
J C
JC
Department of Medicine, Institut de Investigació Biomèdica August Pi i Sunyer, Spain.
Fernández
M
M
Bernadich
C
C
De Lacy
A M
AM
García-Pagán
J C
JC
Bosch
J
J
Rodés
J
J
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005934:Glucagon / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011167:Portacaval Shunt, Surgical; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D013237:Stereoisomerism; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D005934:Glucagon; D008729:Methoxamine; D019331:NG-Nitroarginine Methyl Ester