Higher viscosity participates in the regulation of coronary flow via nitric oxide and indomethacin-sensitive contracting factor

Abstract

Few studies have reported on the association of viscosity with coronary circulation. We evaluated the change in coronary flow after dextran was added to a perfusion solution to increase viscosity in isolated rat hearts. We also measured NOx- production induced by the change in shear stress in the coronary effluent, as a marker of NO synthesis. The baseline coronary flow was not influenced by the presence of either the cyclooxygenase inhibitor indomethacin, the thromboxane A2 (TXA2)-prostaglandin H2 (PGH2) receptor antagonist ONO-3708, or the TXA2 synthase inhibitor OKY-046. After exposure to solution containing 0.5% dextran, the coronary flow first decreased and then gradually increased until 10 min. The initial decrease in coronary flow was inhibited by indomethacin, ONO-3708, and OKY-046 individually. The gradual increase was completely inhibited by the NO inhibitor L-NAME, but not by indomethacin or ONO-3708. OKY-046 partially inhibited the increase. NOx- levels in the effluent were higher after the dextran solution was administered, and the increased NOx- levels were inhibited by L-NAME. The increased NOx- levels were not inhibited by inhibitors of the cyclooxygenase pathway. It appears that a higher viscosity of perfusion solution induced a gradual increase in NO production and was associated with increased production of indomethacin-sensitive contracting factor.

Cardiac mechanoenergetic cost of elevated plasma viscosity after moderate hemodilution

“…The endothelium is capable of producing a large variety of different molecules, agonists and antagonists (NO, prostaglandins, endothelin, to name a few), balancing the effects in both directions. Isolated heart studies have demonstrated that higher viscosity, with the perfusion solution, induced the NO production [17]. Several studies have reported that an increase in endothelial NO synthase levels augments venous return or preload [9, 20, 27], and an enhancement of shear stress by increasing fluid viscosity at a given shear rate increases eNOS expression in endothelial cell culture and in vivo [34, 36–38].…”

“…In response to the decrease in Hct, cardiac output (CO) increases due to reduction in vascular resistance and to maintain oxygenation [9, 11, 14, 19]. Changes in blood viscosity directly affect vascular wall shear stress, and the synthesis of vascular endothelial shear dependent mediators, such as nitric oxide (NO) [17, 21, 22, 34, 37]. Mechanistically, an acute decrease in Hct paired with an increase in plasma viscosity can partially preserve whole blood viscosity.…”

Tissue oxygenation after exchange transfusion with ultrahigh-molecular-weight tense- and relaxed-state polymerized bovine hemoglobins

“…The compensatory mechanisms responding to the acute decrease in Hct involve the increase of cardiac output due to a reduction in vascular resistance due to a lower blood viscosity (10,14,18,23). During hemodilution, blood viscosity is an important factor in the responses of the cardiovascular system, as it affects endothelial shear stress, which activates the synthesis of vascular autocoids, such as prostacyclin and NO (22,26,27,35,42). Beyond the moderate hemodilution level, exchange transfusion using PolybHb at 10 g/dl increases blood O 2 content and plasma viscosity; however, blood viscosity remains lower than nonhemodiluted blood.…”

Improving cardiac function with new-generation plasma volume expanders

“…This mechanical signal regulates endothelial nitric oxide (NO) synthase, which generates NO in blood vessels and is involved with regulating vascular tone by inhibiting smooth muscle contraction and platelet aggregation. [9, 24] Endothelial NO synthase permits the rapid adjustments of NO release in response to changes in blood flow and shear stress. In our study, we speculate that the increase in blood flow due to higher CO after hemodilution and resuscitation with PEG-HSA increases shear stress on vascular endothelial cells and stimulates the generation of NO producing vascular relaxation and explaining the decrease in SVR.…”