Sodium tanshinone IIA sulfonate increased intestinal hemodynamics without systemic circulatory changes in healthy newborn piglets.
In traditional Chinese medicine, tanshinone IIA is a lipid-soluble component of Danshen that has been widely used for various cardiovascular and cerebrovascular disorders, including neonatal asphyxia. Despite promising effects, little is known regarding the hemodynamic effects of tanshinone IIA in newborn subjects. To examine the dose-response effects of sodium tanshinone IIA sulfonate (STS) on systemic and regional hemodynamics and oxygen transport, 12 newborn piglets were anesthetized and acutely instrumented for the placement of femoral arterial and venous, pulmonary arterial catheters to measure mean arterial, central venous, and pulmonary arterial pressures, respectively. The blood flow at the common carotid, renal, pulmonary, and superior mesenteric (SMA) arteries were continuously monitored after treating the piglets with either STS (0.1-30 mg/kg iv) or saline treatment (n = 6/group). To further delineate the underlying mechanisms for vasorelaxant effects of STS, in vitro vascular myography was carried out to compare its effect on rat mesenteric and carotid arteries (n = 4-5/group). STS dose-dependently increased the SMA blood flow and the corresponding oxygen delivery with no significant effect on systemic and pulmonary, carotid and renal hemodynamic parameters. In vitro studies also demonstrated that STS selectively dilated rat mesenteric but not carotid arteries. Vasodilation in mesenteric arteries was inhibited by apamin and TRAM-34 (calcium-activated potassium channel inhibitors) but not by meclofenamate (cyclooxygenase inhibitor) or N-nitro-l-arginine methyl ester hydrochloride (nitric oxide synthase inhibitor). In summary, without significant hemodynamic effects on newborn piglets, intravenous infusion of STS selectively increased mesenteric perfusion in a dose-dependent manner, possibly via an endothelium-derived hyperpolarizing factor vasodilating pathway.
Liu
Jiangqin
J
Departments of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Morton
Jude
J
Miedzyblocki
Margaret
M
Lee
Tze Fun
TF
Bigam
David L
DL
Fok
Tai Fai
TF
Chen
Chao
C
Lee
Shoo K
SK
Davidge
Sandra T
ST
Cheung
Po-Yin
PY
D000818:Animals; D000831:Animals, Newborn; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017536:Carotid Artery, Common / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D007422:Intestines / Q000098:blood supply*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009213:Myography; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D002317:Cardiovascular Agents; D016861:Cyclooxygenase Inhibitors; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; D026902:Potassium Channel Blockers; C024894:tanshinone II A sodium sulfonate; D019001:Nitric Oxide Synthase; D010100:Oxygen