No abstract

1 The signal transduction pathways involved in kinin B 2 receptor-related vasodilation were investigated in rat isolated perfused kidneys. During prostaglandin F 2a or KCl-induced constriction, the vasodilator response to a selective B 2 receptor agonist, Tyr(Me) BK by more than 60%, while inhibition of the cannabinoid CB 1 receptor (SR 141716A) had only a moderate eect. 5 Acetylcholine induced a concentration-dependent relaxation with characteristics nearly similar to the response to Tyr(Me) 8 BK. In contrast, the relaxation elicited by sodium nitroprusside was potentiated in the absence of NO (L-NOARG or removal of endothelium) but remained unchanged otherwise. 6 These results indicate that the activation of kinin B 2 receptors in the rat isolated kidney elicits an endothelium-dependent vasorelaxation, mainly dependent on the activation of charybdotoxinsensitive Ca 2+ -activated K + channels. In addition, cytochrome P450 derivatives appear to be involved.

Epidemiological and clinical studies suggest that air pollution, in particular ambient particulate matter (PM), increases mortality in patients with cardiovascular disease (CVD). Several in vivo studies have shown an increase of blood pressure by PM, but so far the mechanism or responsible particle-component has not been elucidated. We exposed small mesenteric rat artery (SMRA) and rat aorta to ambient particles (EHC-93) to test the ability of ambient particles to modify the vascular tone of different vessel types. PM suspensions (10-100 microg/ml) and filtrates containing only the water-soluble components failed to modify the resting tension of either the aorta or SMRA. However, PM did elicit a dose-dependent vasorelaxation in phenylephrine precontracted SMRA and aorta. The effect of the PM suspensions was higher than that of PM filtrate (without particles). The relaxation was already visible at 10 microg/ml, and the difference with filtrate became significant at 100 microg/ml for aorta (maximal relaxation E(max) = 18% vs. 12% PM filtrate) and as low as 30 microg/ml for SMRA (E(max) = 13% vs. 5% PM filtrate). Although the effect of PM was biggest in aorta, the concentration to cause half of the maximal effect (EC(50)) of suspension and filtrate was the same in both capacity (aorta) and resistance vessels (SMRA). The main difference seen between SMRA and aorta was that PM did not modify the phenylephrine-induced dose-response vasoconstriction in SMRA, while it did do so in the aorta. In conclusion, the in vitro exposure of precontracted blood vessels to ambient PM results in an acute vasorelaxation, which is in contrast to the observation that PM can cause increased blood pressure. Dose calculations show that the elevation of blood pressure observed in vivo is not likely due to direct effects of particles or constituents. We therefore suggest that the in vivo effect of PM on vasoconstriction acts through other pathways, such as the central nervous system.