Sphincters of canine hepatic sublobular veins respond to endothelin-1 and 3

Abstract

 The dog has been used repeatedly as a model in liver transplantation research. The microcirculation and its regulatory mechanisms play a crucial role during ischemia and reperfusion. Little is known about the role of venous sphincters in regulating blood flow in the dog liver. Hence, we performed this study to elucidate their potential role in regulating local blood flow. In 14 dogs mean systemic (MSP) and mean portal venous pressure (MPP) were measured. Light and electron microscopy (scanning and transmission) of tissue sections and vascular corrosion casts were used to elucidate the microvascular morphology. Immunocytochemistry was applied to identify smooth muscle cells and the innervation of venous sphincters. Endothelins 1 and 3 were injected to find whether the hepatic venous sphincters are sensitive to these vasoactive agents. Tufts of smooth muscle cells were found in the sublobular veins (SLV; 100 to 250 µm in diameter), that reduced the luminal diameters of veins by 34%. Nerve endings were not observed close to these venous sphincters. The MSP and MPP were 75.3±2.4 mmHg and 8.9±0.95 mmHg, respectively. Treatment with 1.0 µg/kg of endothelin-1 (ET-1) significantly increased the MSP, the MPP and the percentage of focal venous sphincter contraction by 39% (105±4.7 mmHg), 43% (12.8±1.7 mmHg) and 57% (53.5±4.7), respectively (P <0.01). Treatment with ET-3 caused a significant (P <0.01) decrease in the MSP, the MPP and the percentage of sphincter contraction by 19% (61.0±2.2 mmHg), 39% (5.8±2.9 mmHg) and 38% (20.9%±3.15). Sinusoids did not contain sphincters. Hepatic arterioles and central veins were not affected by ET-treatment. The contraction of SLV sphincters correlated with increases in MPP (r=0.81, P <0.01) and was related to the MSP (r=0.67, P <0.01). These data show that the smooth muscle sphincters in SLV of the dog liver are involved in the local regulation of blood flow and that these sphincters are stimulated by non-neurogenic mechanisms. These sphincters contract in response to ET-1 and relax in response to ET-3. Since ET-1 is released during and/or causes inflammation, e.g., during ischemia and reperfusion, its antagonists might be of benefit during transplantation reperfusion of liver.