Shear-induced modulation of vasoconstriction in the hepatic artery and portal vein by nitric oxide.

Abstract

The effect of shear stress on nitric oxide (NO)-mediated suppression of sympathetic nerve (2-6 Hz)- and norepinephrine (0.5 microgram.kg-1.min-1)-induced vasoconstriction in the hepatic artery (HA) and portal vein (PV) was studied using a perfusion circuit to regulate blood pressure and flow in the cat liver in situ. Holding flow constant resulted in increased shear stress during constriction; holding pressure steady prevented changes in shear stress. When shear stress was allowed to rise, the vasoconstriction (indicated by elevation in perfusion pressure) in response to nerve stimulation and norepinephrine was significantly potentiated after NO synthase blockade using NG-nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg iv) in both the HA and PV (response to nerves: HA control 28.8 +/- 6.5 mmHg, L-NAME 62.7 +/- 14.6 mmHg; PV control 1.5 +/- 0.5 mmHg, L-NAME 3.3 +/- 0.5 mmHg; response to norepinephrine: HA control 32.4 +/- 9.0 mmHg, L-NAME 60.3 +/- 8.0 mmHg; PV control 1.3 +/- 0.3 mmHg, L-NAME 3.4 +/- 0.7 mmHg). The potentiation was reversed by L-arginine (75 mg/kg). When shear stress was held constant by maintaining constant perfusion pressure, L-NAME did not cause potentiation of vasoconstriction. The data are consistent with the hypothesis that elevated shear stress in the hepatic blood vessels leads to NO-dependent postjunctional modulation of vasoconstriction.