Alterations of intracellular calcium concentration and nitric oxide generation in pulmonary artery endothelium after subarachnoid hemorrhage of the rabbit.
The present study was designed to investigate whether endothelial intracellular calcium concentration ([Ca(2+)](i)), endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) generation altered in association with impaired endothelium-dependent relaxation (EDR) in pulmonary artery (PA) specimens from experimental subarachnoid hemorrhage (SAH) rabbits. Injecting non-heparinized autologous arterial blood into cisterna magna induced the SAH. Simultaneous measurements of endothelial [Ca(2+)](i) and isometric tension of PA specimens were performed using fura 2. The subjects included normal control rabbits (group N), SAH rabbits with normal EDR (group A) and with impaired EDR (group B). When treated with 10(-7) M acetylcholine (ACh), endothelial [Ca(2+)](i) was significantly lower in group B (74.1+/-8.5 nM) than that in groups A (153.0+/-28.0 nM, p<0.05) and N (184.8+/-27.8 nM, p<0.01). Basal and ACh-stimulated cyclic GMP productions as a marker of NO generation were also significantly (p<0.005) decreased in group B as compared to those in the other two groups. Meanwhile, there were no differences in eNOS activity per se among the three groups. These results suggest that the attenuated endothelial [Ca(2+)](i) elevation leads to the impaired NO generation in PA endothelium, which in turn impairs the EDR and possibly increases the vascular resistance of PA following SAH.
Kubota
Yoshihiro
Y
Department of Neurosurgery, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Isotani
Eiji
E
Mizuno
Yusuke
Y
Ohno
Kikuo
K
Azuma
Hiroshi
H
D000109:Acetylcholine / Q000008:administration & dosage; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D016257:Fura-2; D007537:Isometric Contraction; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000503:physiopathology; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*
D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2