Biomedical subjects

Herta M Crauwels

Publications and source records attributed to Herta M Crauwels.

2 recordsLinked to original sources

PubMed2005

Pharmacological characterization of nucleotide P2Y receptors on endothelial cells of the mouse aorta.

Nucleotides regulate various effects including vascular tone. This study was aimed to characterize P2Y receptors on endothelial cells of the aorta of C57BL6 mice. Five adjacent segments (width 2 mm) of the thoracic aorta were mounted in organ baths to measure isometric force development. Nucleotides evoked complete (adenosine 5' triphosphate (ATP), uridine 5' triphosphate (UTP), uridine 5' diphosphate (UDP); >90%) or partial (adenosine 5' diphosphate (ADP)) relaxation of phenylephrine precontracted thoracic aortic rings of C57BL6 mice. Relaxation was abolished by removal of the endothelium and was strongly suppressed (>90%) by inhibitors of nitric oxide synthesis. The rank order of potency was: UDP approximately UTP approximately ADP>adenosine 5'-[gamma-thio] triphosphate (ATPgammaS)>ATP, with respective pD2 values of 6.31, 6.24, 6.22, 5.82 and 5.40. These results are compatible with the presence of P2Y1 (ADP>ATP), P2Y2 or P2Y4 (ATP and UTP) and P2Y6 (UDP) receptors. P2Y4 receptors were not involved, since P2Y4-deficient mice displayed unaltered responses to ATP and UTP. The purinergic receptor antagonist suramin exerted surmountable antagonism for all agonists. Its apparent pKb for ATP (4.53+/-0.07) was compatible with literature, but the pKb for UTP (5.19+/-0.03) was significantly higher. This discrepancy suggests that UTP activates supplementary non-P2Y2 receptor subtype(s). Further, pyridoxal-phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) showed surmountable (UTP, UDP), nonsurmountable (ADP) or no antagonism (ATP). Finally, 2'-deoxy-N6-methyladenosine3',5'-bisphosphate (MRS2179) inhibited ADP-evoked relaxation only. Taken together, these results point to the presence of functional P2Y1 (ADP), P2Y2 (ATP, UTP) and P2Y6 (UDP) receptors on murine aorta endothelial cells. The identity of the receptor(s) mediating the action of UTP is not fully clear and other P2Y subtypes might be involved in UTP-evoked vasodilatation.

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PubMed2003

Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI.

OBJECTIVE: Apolipoprotein E-deficient mice (apoE(-/-)) on a regular diet become hypercholesterolemic and develop atherosclerosis, but endothelium-dependent relaxation remains undisturbed for up to 6 months. We investigated whether vasomotor dysfunction develops in aged apoE(-/-), whether the defect was systemic (hypercholesterolemia-dependent) or focal (plaque-related), and the effect of human apolipoprotein AI transgenesis (apoAI/E(-/-)). METHODS: Arteries of apoE(-/-) (n=5), apoAI/E(-/-) (n=6) and C57Bl/6J (WT, n=4) mice (18 months) were systematically dissected for isometric tension recording and subsequent morphometry. RESULTS: Acetylcholine (ACh)-induced relaxation was impaired (P<0.01) in atherosclerotic segments of apoE(-/-) (26+/-14%) as compared to WT mice (93+/-2%). Similar reduced (P<0.01) responses to adenosine 5'-triphosphate (apoE(-/-) 38+/-14, WT 94+/-3%) and the calcium ionophore A23187 (apoE(-/-) 19+/-6%, WT 97+/-2%) pointed to a post-receptor defect. Indeed, responses to exogenous nitric oxide were impaired in atherosclerotic segments as well (apoE(-/-) 71+/-7%, WT 92+/-1%, P<0.05). Furthermore, relaxations inversely correlated with plaque size (ACh r(s)=-0.74, P<0.01). In adjacent plaque-free segments however, responses to ACh (apoE(-/-) 92+/-3%, WT 97+/-1%) and all other agents were preserved, despite the prolonged hypercholesterolemia. ApoAI improved vasomotor responses in atherosclerotic segments. However, negative correlations between maximal relaxation and plaque area remained in apoAI/E(-/-) mice (ACh r(s)=-0.67, P<0.01). Indeed, covariate analysis of variance did not point to direct protection of vasomotor function by apoAI when the smaller lesions were taken into account. CONCLUSIONS: Endothelial dysfunction in apoE(-/-) mice is not affected by hypercholesterolemia alone, but is strictly associated with plaque formation. Human apoAI transgenesis-known to raise HDL-attenuated atherogenesis, thereby indirectly improving relaxation responses in apoE(-/-) mice.

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