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1 To characterize the prostanoid receptors on human pulmonary smooth muscle involved in vasodilatations, isolated arteries and veins were contracted with norepinephrine (10 mM) and vessels were subsequently challenged with dierent prostanoid-receptor agonists in the absence or presence of selective antagonists. 2 Prostaglandin D 2 (PGD 2 ) and the selective DP-receptor agonist, BW245C, induced relaxations in the contracted human pulmonary venous preparations. The pD 2 values were: 6.88+0.11 (n=17) and 7.31+0.12 (n=5), respectively. The relaxant responses induced by PGD 2 were reduced by the selective DP-receptor antagonist, BWA868C, and the estimated pA 2 value was 7.84+0.16 (n=4). PGD 2 and BW245C did not relax contracted human pulmonary arteries. 3 The selective IP-receptor agonists, iloprost and cicaprost, both induced relaxations in the contracted human vascular preparations. The pD 2 values for iloprost were: 7.84+0.08 (n=6) and 8.25+0.06 (n=4) and for cicaprost: 8.06+0.12 (n=5) and 8.11+0.09 (n=5) in arteries and veins respectively. 4 Prostaglandin E 2 (PGE 2 ) and the EP 2 /EP 3 -receptor agonist, misoprostol, partially relaxed the contracted venous preparations and the pD 2 values were: 8.10+0.15 (n=15) and 6.24+0.33 (n=3), respectively. These relaxations suggest the presence of an EP receptor in the human pulmonary veins. The contracted human pulmonary arteries did not relax when challenged with PGE 2 . 5 In human pulmonary venous preparations, the PGE 2 -induced relaxations were neither modi®ed by treatment with TP/EP 4 -receptor antagonist, AH23848B (10 and 30 mM, n=6), nor by the DP/ EP 1 /EP 2 -receptor antagonist, AH6809 (3 mM, n=6). 6 These data suggest that the relaxation induced by prostanoids involved DP-, IP-receptors and to a lesser extent an EP-receptor on human pulmonary venous smooth muscle. In contrast, only the IPreceptor is involved in the prostanoid induced relaxations on human pulmonary arterial smooth muscle.

1 To characterize the prostanoid receptors (TP, FP, EP 1 and/or EP 3 ) involved in the vasoconstriction of human pulmonary veins, isolated venous preparations were challenged with di erent prostanoid-receptor agonists in the absence or presence of selective antagonists. 2 The stable thromboxane A 2 mimetic, U46619, was a potent constrictor agonist on human pulmonary veins (pEC 50 =8.60+0.11 and E max =4.61+0.46 g; n=15). The a nity values for two selective TP-antagonists (BAY u3405 and GR32191B) versus U46619 were BAY u3405: pA 2 =8.94+0.23 (n=3) and GR32191B: apparent pK B =8.25+0.34 (n=3), respectively. These results are consistent with the involvement of TP-receptor in the U46619 induced contractions. 3 The two EP 1 -/EP 3 -agonists (17-phenyl-PGE 2 and sulprostone) induced contraction of human pumonary veins (pEC 50 =8.56+0.18; E max =0.56+0.24 g; n=5 and pEC 50 =7.65+0.13; E max =1.10+0.12 g; n=14, respectively). The potency ranking for these agonists: 17-phenyl-PGE 2 4sulprostone suggests the involvement of an EP 1 -receptor rather than EP 3 . In addition, the contractions induced by sulprostone, 17-phenyl-PGE 2 and the IP-/EP 1 -agonist (iloprost) were blocked by the DP-/EP 1 -/EP 2 -receptor antagonist (AH6809) as well as by the EP 1 antagonist (SC19220). 4 PGF 2a induced small contractions which were blocked by AH6809 while¯uprostenol was ine ective. These results indicate that FP-receptors are not implicated in the contraction of human pulmonary veins. 5 These data suggest that the contractions induced by prostanoids involved TP-and EP 1 -receptors in human pulmonary venous smooth muscle.

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1 Iloprost and cicaprost (IP-receptor agonists) induced relaxations in the histamine-(50 mM) contracted human bronchial preparations (pD 2 values, 6.63+0.12 and 6.86+0.08; E max values, 90+04 and 65+08% of the papaverine response for iloprost (n=6) and cicaprost (n=3), respectively).2 Prostaglandin E 2 (PGE 2 ) and misoprostol (EP-receptor agonist) relaxed the histamine-contracted human bronchial preparations (pD 2 values, 7.13+0.07 and 6.33+0.28; E max values, 67+04 and 57+08% of the papaverine response for PGE 2 (n=14) and misoprostol (n=4), respectively). In addition, both relaxations were inhibited by AH6809 (DP/EP 1 /EP 2 -receptor antagonist; 3 mM; n=5 ± 6). 3 The PGE 2 -induced relaxations of human bronchial preparations were not modi®ed by treatment with AH23848B (TP/EP 4 -receptor antagonist; 30 mM; n=4). 4 The contracted human bronchial preparations were signi®cantly relaxed by prostaglandin D 2 (PGD 2 ) or by BW245C a DP-receptor agonist. However, these responses did not exceed 40% of the relaxation induced by papaverine. In addition, the relaxations induced by PGD 2 were signi®cantly inhibited by treatment with a DP-receptor antagonist BWA868C (0.1 mM; n=3). 5 These data suggest that the relaxation of human isolated bronchial preparations induced by prostanoids involved IP-, EP 2 -and to a lesser extent DP-receptors but not EP 4 -receptor.

Objective:Whereas circulating levels of C-reactive protein (CRP) have been associated with, for example, arterial stiffness, subclinical atherosclerosis and metabolic syndrome, other inflammatory biomarkers with potential interest for these conditions may not be measurable systemically. The predictive value of salivary biomarkers in these contexts has remained largely unexplored. The aim of the present study was to establish the association of different salivary biomarkers of inflammation with subclinical cardiovascular disease.Methods:Two hundred and fifty-nine individuals were included in the study. Saliva and plasma samples were collected, and each individual underwent carotid ultrasound and measures of pulse wave velocity and blood pressure. Medical history of previous cardiovascular disease, current medications and smoking were collected by questionnaire.Results:Salivary levels of CRP, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), matrix metalloproteinase 9 (MMP-9), creatinine and lysozyme were measured. Salivary levels of CRP were significantly correlated with plasma levels (r = 0.73, P < 0.0001). In an age-adjusted and sex-adjusted analysis, salivary CRP was significantly and positively correlated with mean arterial blood pressure, pulse pressure, pulse wave velocity, BMI, metabolic syndrome, waist-to-hip ratio and intima–media thickness. Increasing age and sex-adjusted salivary CRP tertiles were in addition associated with carotid plaques. In a multivariate analysis, CRP and MMP-9 were associated with intima–media thickness, LTB4 and PGE2 with arterial stiffness, and lysozyme with hypertension.Conclusion:Saliva may represent an alternative mean for evaluation of cardiovascular risk.