Diseases such as hypertension, atherosclerosis, hyperlipidemia, and diabetes are associated with vascular, functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. The role of vascular endothelium in modulating vascular tone and maintaining cardiovascular homeostasis in blood vessels, through the production of an array of both relaxant (e.g., nitric oxide [NO], prostacyclin) and constrictor factors (such as thromboxane, endothelin), has been widely reported.
1-4)The development of hypertension is accompanied by changes in the rheological properties of blood, particularly by an increased red blood cell (RBC) aggregation, leading to further pathological complications. Plasma viscosity contributes to the cardiovascular risks and may be of special importance in cases of reduced blood flow, as commonly occurs in patients with advanced atherosclerosis, 5) and it is also related to the extension of coronary heart disease.6,7) Effects of rheological properties of blood on thrombogenesis and atherosclerosis has been cited in several reports. [8][9][10] We previously investigated blood pressure (BP) lowering-effects of the dietary astaxanthin (ASX-O) in spontaneously hypertensive rats (SHR).11) The current study was designed to investigate the antihypertensive mechanisms of action of ASX-O by investigating its effects on vascular reactivity in the SHR. Contractile and relaxant responses of the vascular system were studied on aortic rings from ASX-Otreated SHR. Moreover, the effects of ASX-O on blood fluidity and rheology were evaluated by microchannel transit time analysis.
MATERIALS AND METHODS
General ProceduresMale SHR (7 weeks old) were used in this study. The animals were obtained from colonies of specific pathogen-free rats maintained by Japan Shizuoka Laboratory Company (Japan SLC, Shizuoka, Japan). Housing conditions were thermostatically maintained at 24Ϯ1°C with constant humidity (60%) and lighting (12 h light/dark cycle, light on: 07:30-19:30). The animals were housed for at least 1 week before the experiments and fed a normal diet (Lab MR, NOSAN, Yokohama, Japan) and water given ad libitum. Body weights were measured daily during the experimental period. ASX-O, composed of 5.5% astaxanthin (ASX) in edible oil base, was obtained from Fuji Chemical (Fuji Chemical Industry Co., Ltd., Toyama, Japan) and dissolved and diluted in olive oil (Wako Pure Chemicals, Osaka, Japan). Administered doses were calculated as ASX in the dietary ASX-O. The animals were divided into two groups (8 rats/group) and were treated daily for 7-9 weeks. One group was administered ASX (5 mg/kg/d, p.o.) and the other one was similarly treated with olive oil (1 ml/kg/d).All experimental procedures were performed in accordance with the standards established by the 'Guide for the Care and Use of Laboratory Animals at Toyama Medical and Pharmaceutical University'.
Measurement of BP and Heart Rate (HR) in Conscious RatsArterial BP and HR were determined by a tail cuff system. The rats we...