Nitric oxide modulates microvascular permeability.

Area of Science:

• Physiology
• Vascular Biology
• Gastroenterology

Background:

• Nitric oxide (NO) is crucial for regulating vascular tone and leukocyte behavior.
• Inhibitors of NO production are known to increase leukocyte adherence in postcapillary venules.

Purpose of the Study:

• To investigate if inhibiting NO production causes vascular protein leakage and increased microvascular permeability in the feline small intestine.
• To determine the role of adherent leukocytes in these NO inhibition-induced microvascular changes.

Main Methods:

• Administration of NG-nitro-L-arginine methyl ester (L-NAME), a NO synthesis inhibitor, in feline models.
• Measurement of microvascular fluid and protein fluxes, capillary pressure, and permeability index.
• Use of nitroprusside to reverse L-NAME effects.
• Pretreatment with anti-CD11/CD18 monoclonal antibody (MoAb IB4) to assess leukocyte involvement.

Main Results:

• L-NAME significantly increased microvascular fluid and protein fluxes, indicating enhanced permeability, while capillary pressure remained unchanged.
• The permeability index (1 - sigma d) increased significantly after L-NAME infusion.
• L-NAME-induced microvascular alterations were fully reversed by nitroprusside.
• MoAb IB4 attenuated the later phase of protein leakage but did not prevent the initial increase, suggesting both leukocyte-dependent and -independent mechanisms.

Conclusions:

• Inhibition of endothelial NO production leads to a reversible increase in microvascular protein efflux in the feline small intestine.
• Both leukocyte-dependent and -independent pathways contribute to the increased vascular permeability observed upon NO synthesis inhibition.