Hepatic Microvascular Regulatory Mechanisms. II. Cholinergic Mechanisms

Abstract

Several cholinergic agonists and their antagonists were administered topically at various concentrations (lo-'' to gm per ml) to the livers of anesthetized Sprague-Dawley rats. Changes in the microvasculature were measured for a period of 15 min using in uiuo microscopic methods. The influence of cholinergic agonists on hepatic mast cells was determined by histochemical methods. Cholinergic agonists elicited constriction of portal venules, sinusoids, and terminal hepatic (central) venules accompanied within 5 to 20 sec by the adherence of platelets and leukocytes to the endothelial lining of these vessels. These responses were not observed in hepatic arterioles or hepatic (sublobular) venules. However, the responses drastically altered cellular flow through all segments of the microvasculature. The drugs were effective in the following ranking: bethanechol > pilocarpine > carbachol. Vascular responses were not antagonized by atropine; phentolamine modified the constrictor response of portal venules but of no other microvascular segment. These results suggest that the responses were not mediated by cholinergic (muscarinic) receptors and that the constriction of portal venules was caused by the chemical activation of a-adrenergic receptors. Histochemical methods revealed that pilocarpine and bethanechol also elicited a significant decrease in the number of visible mast cells suggestive of degranulation and the release of serotonin, histamine, and other polyanions (e.g., heparin) from these cells. Release occurred within the same period of time as the microvascular alterations (15 min). These data provide additional evidence that mast cell constituents and adrenergic mechanisms are involved in hepatic cholinergic mechanisms.Only limited information has been reported concerning the direct effects produced by cholinergic mechanisms on the hepatic microvasculature. Koo and Liang (1-4) report that vagal stimulation and the intraportal infusion of acetylcholine and cholinergic agonists produce dilation of sinusoids. Since this response was antagonized by atropine and physostigmine, they suggested the existence of cholinergic receptors in sinusoids. However, Koo and Liang did not study the effect of cholinergic stimulation on microvascular segments other than sinusoids. Their observations of the microvasculature also were restricted to a brief interval of time (5 sec) in order to limit supervening effects secondary to alterations in systemic arterial and portal venous pressures. As a result, there is little knowledge about the distribution of cholinergic receptors on each segment of the hepatic microvasculature, and the relative sensitivities of these segments to cholinergic substances and their antagonists.The indirect or secondary effects caused by cholinergic mechanisms also are poorly understood. T o date, only a few studies have considered that such indirect effects may have profound influences on microvascular regulatory mechanisms. Several studies suggest that there is considerable interaction among topically appli...

Mast Cell Degranulation, Hepatic Glycogen Depletion, and Hyperglycemia in Compound 48/80 or Pilocarpine-Treated Rats

“…with these substances. Changes in hepatic microvasculature and in the number of Falck-Hillarppositive cells counted in hepatic tissue are reported in another manuscript (3).…”

“…In 14 of these rats, direct blood pressure was monitored on a Beckman R-611 Dynograph. To evaluate the direct effect of Compound 48/80, or pilocarpine, or Ringer's solution on hepatic microvasculature, glycogen content, and mast cell integrity, livers of 15 rats (70 to 90 gm) were treated topically with 10 pg per 0.1 ml Compound 48/80 (five rats), 100 pg per 0.1 ml pilocarpine-HC1 (five rats), or 0.1 ml Ringer's solution (five rats) according to the in uiuo microscopic methods described by McCuskey et al (10) and Reilly et al (3,11).…”

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

“…Accordingly, the description of leukocyte adherence (661) and phagocytosis (54) has been only qualitative in nature. Even in case of quantitative analysis of the transilluminated liver (415,661,662), results should be interpreted with caution, because the areas within the liver periphery present with a considerable extent of nonperfused sinusoids already under baseline conditions (167) and cannot be considered representative for the liver microcirculation in general.…”

Vasoconstrictor effect of acetylcholine in veins of the liver

“…Paradoxically, Ach and cholinergic agonists constrict liver veins. This effect was observed in situ on rats and in vitro on isolated strips of the portal and mesenteric veins [1,6,10,11]. Specifically, the constrictor response to stimulation of cholinergic nerve terminals or injection of Ach was observed in hepatic vein, posterior vena cava, and some other liver veins, and in pulmonary vessels [3].…”