Cristina C. Trandafir

PARTICIPATION OF VASOPRESSIN IN THE DEVELOPMENT OF CEREBRAL VASOSPASM IN A RAT MODEL OF SUBARACHNOID HAEMORRHAGE

1. Previous studies have suggested the involvement of arginine vasopressin (AVP) and inflammation in the development of cerebral vasospasm after subarachnoid haemorrhage (SAH). The aim of the present study was to clarify the role of AVP in the arterial narrowing following cerebral haemorrhage by examining the effect of SR 49059 (a V1 receptor antagonist) on the diameter of rat basilar artery exposed to SAH. The effect of the 5‐lipoxygenase inhibitor ZM 230487 on AVP‐induced contraction of rat basilar arteries was also investigated.

Involvement of endothelial cyclo-oxygenase metabolites in noradrenaline-induced contraction of rat coronary artery.

1. Noradrenaline (NA; 0.3 µmol/L) caused a contraction of the rat coronary artery that markedly increased in the presence of the nitric oxide synthase (NOS) inhibitor NG‐nitro‐l‐arginine methyl ester (l‐NAME; 100 µmol/L) and arachidonic acid (1 µmol/L; P < 0.05).

Cysteinyl leukotrienes and leukotriene B4 mediate vasoconstriction to arginine vasopressin in rat basilar artery

1. Arginine vasopressin (AVP) has been reported to be involved in the development of cerebral vasospasm after haemorrhage and cerebral oedema following ischaemia. Endogenously produced 5‐lipoxygenase metabolites are able to contract isolated endothelium‐preserved arterial strips and modulate vascular permeability. The present study addresses the role of 5‐lipoxygenase and its products, namely cysteinyl leukotrienes (CysLTs) and leukotriene (LT) B4, in the contraction induced by AVP in rat basilar artery.

Effects of the Experimental Subarachnoid Hemorrhage on the Eicosanoid Receptors in Nicotine-induced Contraction of the Rat Basilar Artery

BACKGROUND Smoking is one of the most important risk factors for subarachnoid hemorrhage (SAH). The purpose of this study was to investigate the influence of experimental SAH and arachidonic acid metabolites on nicotine-induced contraction in the rat basilar artery. METHODS Rats were killed at 1 hour and 1 week after SAH, and the basilar artery was isolated and cut into a spiral strip. The effects of various eicosanoid receptor antagonists on nicotine-induced contraction in the rat basilar artery were investigated. RESULTS Antagonists of thromboxane A2 (TXA2) and cysteinyl leukotriene (CysLT) receptors did not affect nicotine-induced contraction. In contrast, the antagonists of leukotriene B4 (LTB4) receptors (BLT1 and BLT2) attenuated the nicotine-induced contraction in the rat basilar artery. We also observed that SAH did not influence the effect of TXA2, LTB4, and CysLTs receptor antagonists on the nicotine-induced contraction. These results suggest that TXA2 and CysLTs are not involved in nicotine-induced contraction, while LTB4 potentates this contraction in rat basilar artery. CONCLUSIONS BLT2 receptor seemed to be more involved in the nicotine-induced contraction than the BLT1 receptor. SAH did not affect the involvement of eicosanoids in the nicotine-induced contraction of the rat basilar artery. The present study shows the involvement of some of the arachidonic acid metabolites into signaling pathways of nicotine-induced contraction. It will serve to improve therapeutic interventions of SAH and suggests a promising approach to protect the cerebral vasculature of cigarette smokers.

Influence of experimental subarachnoid hemorrhage on nicotine-induced contraction of the rat basilar artery in relation to nicotinic acetylcholine receptors, calcium, and potassium channels.

BACKGROUND Cigarette smoking is associated with symptomatic vasospasm after subarachnoid hemorrhage (SAH). METHODS Rat basilar arteries of a normal group and SAH groups (1 hour, 2 days, and 1 week) were removed from the brain and cut into spiral preparations. RESULTS A central nervous system (CNS) nicotinic acetylcholine receptor (nAChR) and autonomic ganglionic nAChR antagonist (mecamylamine) and skeletal muscle nAChR antagonist (gallamine) concentration-dependently attenuated the nicotine-induced contraction. An autonomic ganglionic nAChR antagonist (hexamethonium) did not affect nicotine-induced contractions in normal rats or rats with SAH. The various nAChR antagonists showed no significant differences in their effects between normal and SAH (1 hour, 2 days, and 1 week) rats. An L-type Ca(2+) channel antagonist (nifedipine) attenuated the nicotine-induced contraction in a concentration dependent manner. Inhibition by nifedipine was significantly enhanced in the 1-hour and 2-day SAH groups compared with normal and 1-week SAH groups. Levcromakalim showed a greater attenuation of nicotine-induced contraction in SAH (1 hour, 2 days, and 1 week) than in normal rats. CONCLUSIONS Nicotine-induced contraction of the rat basilar artery involved the CNS nAChR subfamily, skeletal muscle nAChR subfamily, and L-type Ca(2+) channel pathways. SAH did not affect any of the subfamilies of nAChR, but the Ca(2+) channel was reduced and the adenosine triphosphate-sensitive K(+) channel was enhanced by SAH.

Noradrenaline-induced contraction mediated by endothelial COX-1 metabolites in the rat coronary artery.

Summary: Noradrenaline‐induced contraction of the rat coronary arteries was significantly augmented by the presence of NG‐nitro‐ L‐arginine methyl ester (L‐NAME) and arachidonic acid. The experiments in the study presented here were undertaken to characterize pharmacologically the augmented noradrenaline‐induced contraction in ring preparations of rat coronary arteries. The contraction was stopped by a chemical remover of endothelium (saponin). Oxygen radical scavengers, superoxide dismutase and catalase, significantly attenuated the contraction. Cyclooxygenase‐1 inhibitors (flurbiprofen, 10‐7 M) attenuated the noradrenaline‐induced contraction and cyclooxygenase‐2 (nimesulide, 10‐7 M) slightly attenuated the contraction. A thromboxane A2 (TXA2) synthetase inhibitor (OKY‐046) and a TXA2 receptor antagonist (S‐1452) did not affect the contraction. Based on these results, it was suggested that the contraction induced by noradrenaline in the rat coronary artery in the presence of L‐NAME and arachidonic acid is endotheliumdependent, and that it involves reactive oxygen species and endothelial cyclooxygenase‐1 metabolites of arachidonic acid.