Endothelial loss of isolated rabbit femoral artery and renal artery was evaluated during in vitro vessel perfusion. Desquamated endothelial cells were captured on millipore filters from the perfusion solution outflow of the vessel in 3 intervals lasting 5 minutes each. In the first 5 minutes of perfusion the endothelial loss was 1 289.2 ± 166.5 cells: in the interval after a 30 minute perfusion 4 967.9 ± 1 428.3 cells were caught on the filters, 3.9 times more than in the first interval. During and after the 2 minutes air bubble perfusion the endothelial catch was 5.5 times greater as compared to the second interval with the average of 27 473 ±6 209.6 cells. The present method of quantification of the endothelial cell loss in the in vitro vessel perfusion experiment makes it possible to obtain informations about the actual state of the endothelial lining and to contribute to more precise evaluation of the modulatory effect of the endothelium on vessel reactivity to pharmacological agents.
It became evident in the present study that carbon tetrachloride (CCl4), in addition to its known liver and renal toxicity, causes serious damage to endothelial cells. The preventive effect of red wine on cardiovascular diseases has been documented in a number of human population studies as well as in animal experimental models. In this study, the endothelium protective effect of polyphenolic compounds isolated from red wine was studied in rats administered 0.5 ml of CCl4/kg body weight intraperitoneally twice a week for 8 weeks. Endothelemia (endothelial cells/10 μl of plasma) was used as the marker of endothelial cell injury in vivo. Chronic CCl4 treatment for 8 weeks lead to a 3-fold increase of free endothelial cells circulating in the blood when compared to the baseline values (2.5±0.3). Parallel oral administration of polyphenols 40 mg/kg/day significantly decreased the endothelemia. Polyphenolic compounds alone did not produce significant changes. Three weeks of spontaneous recovery after the 8-week treatment with CCl4 did not lead to a marked decrease of endothelemia, but the administration of red wine polyphenols during the 3-week period significantly decreased free endothelial cells in the blood. It can be concluded that long-term administration of CCl4 may serve as a useful experimental model of endothelial damage. The red wine polyphenolic compounds exert a powerful protective effect on endothelial cells from the injury caused by CCl4. This effect was documented by decreased endothelemia that corresponded to diminished endothelial cell swelling and detachment evaluated by histology of the vascular intima. The endothelium protective effect may be one of the key factors that contribute to the preventive action of red wine on cardiovascular diseases.
In rats, neonatal administration of monosodium glutamate (MSG) causes serious damage in some hypothalamic and circumventricular areas. The resulting loss of appropriate neurons important for the regulation of blood pressure (BP) may modulate cardiovascular system receptivity in these animals. In the present study, the reactivity of the cardiovascular system to intravenous injection of ai-adrenergic receptor agonist phenylephrine (200 ^g/kg/ml) and angiotensin II (500 ng/kg in 0.6 ml for 2 min) was investigated in adult rats which had been neonatally treated with MSG or vehicle. BP parameters measured directly in conscious cannulated rats were continuously registered using a computerized system. Under basal conditions, MSG-treated rats had slightly lower systolic, diastolic and mean BP with significant differences in pulse pressure (systolic - diastolic BP). In MSG-treated animals, the maximal increase of mean arterial BP after phenylephrine and the duration of BP elevation after both agents were significantly reduced. Slopes of the linear portion of baroreceptor function curves in control and MSG-treated rats did not differ significantly, indicating that baroreflex efficacy was unchanged. The results obtained by perfusion of the hindlimb vascular bed in situ showed that the pressure responses to increasing doses of noradrenaline in MSG-treated rats were reduced. These findings demonstrate that neonatal treatment of rats with MSG lowers the responsiveness of the cardiovascular system, particularly in response to a-adrenergic stimulation. It is suggested that the attenuation of cardiovascular reactivity in MSG-treated rats is, at least partly, caused by diminished vascular responsiveness.