الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
Hemodynamic studies were performed in conscious rats to investigate the mechanisms of the hypertensive and baroreflex depressant effects of CSA in conscious rats. The study first examined the modulatory role of central sympathetic activity and related neuronal circuits of 2 and I1 receptors in the acute hypertensive action of CSA. Experiments were then extended to evaluate the role of central NOS/NO and HO/CO signaling in the hypertensive response to CSA and its interaction with central I1 receptors. Finally, the hypothesis was tested that concurrent exposure to the central sympatholytic drug moxonidine ameliorates the hypertensive and baroreflex depressant effects of chronically administered CSA. Pharmacological evidence was sought to characterize the roles of reflex control of vagal and sympathetic autonomic components and oxidative stress in the CSA-moxonidine hemodynamic interaction. The main results and conclusions of the study are outlined below.
1- Intravenous administration of CSA (20 mg/kg) in conscious freely moving rats produced a rapid increase in BP that continued for the 45 min duration of the study. Ganglionic or α1-adrenoceptor blockade reduced the pressor effect of CSA. Pressor responses to PE were not affected by CSA, thereby ruling out the potential involvement of altered responsiveness to vascular α1-adrenoceptors in CSA hypertension.
2- The hypertensive action of CSA was attenuated in rats pretreated intravenously with the central sympatholytic drugs clonidine (mixed α2/I1-receptor agonist) or moxonidine (selective I1-receptor agonist), in contrast to no effect for guanabenz (selective α2-receptor agonist). A similar inhibition of CSA hypertension was seen after i.c. administration of moxonidine. Blockade of central I1 (efaroxan) but not α2 (yohimbine) receptors abolished the hypertensive and hypotensive responses to CSA and moxonidine, respectively. These findings highlight a preferential interaction of CSA with central circuits of I1 receptors. Apparently, the interruption of tonic inhibitory influences of I1-receptors on central sympathetic tone underlies the CNS-dependent hypertensive effect of CSA