Endothelium-dependent vasodilatory and hypotensive effects of Crotalaria sessiliflora L. in rats.
The aim of the present study was to investigate the vasoactive effect of Crotalaria sessiliflora L. extract (CSE) on rats and its mechanism when combining in vivo and in vitro approaches. CSE (0.5-5 mg/ml) induced concentration-dependent relaxation on endothelium-intact thoracic aortic rings precontracted with phenylephrine (PE, 10(-5) M). This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic strips with either N(G)-nitro-L-arginine (L-NNA, 10(-5) M) or methylene blue (10(-5) M) significantly reduced the relaxation induced by CSE. The endothelium-dependent relaxation caused by CSE was associated with production of cGMP. CSE (5 mg/ml) increased the production of cGMP in endothelium-intact aortic rings and this effect was significantly attenuated by L-NNA (10(-5) M) and methylene blue (10(-5) M). Relaxation in response to CSE in strips precontracted with PGF2alpha (3x10(-5) M) was eliminated by removing extracellular Ca2+ and significantly reduced by pretreatment with ruthenium red (10(-5) M). In in vivo tests, injection of 40 mg/kg of CSE induced an increase in plasma NO production, and this effect was blocked by L-NNA. Furthermore, CSE produced dose-dependent and transient decrease in blood pressure in normotensive rats and this effect was blocked by atropine as well as L-NNA. These findings suggest that CSE induces endothelium-dependent relaxation via NO/cGMP signaling by promoting extracellular Ca2+ influx and the release of Ca2+ from intracellular stores of endothelium, probably due to endothelial muscarinic receptor activation.
Koh
Sang Bum
SB
Safety Assessment Center, Korea Testing and Research Institute for Chemical Industry, Gimpo.
Kang
Myung Hwa
MH
Kim
Tae Su
TS
Park
Hee Woon
HW
Park
Chun Geon
CG
Seong
Yeon Hee
YH
Seong
Ha Jung
HJ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D029864:Crotalaria; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D010936:Plant Extracts; D011976:Receptors, Muscarinic; D014665:Vasodilator Agents; D009569:Nitric Oxide; D006152:Cyclic GMP; D002118:Calcium