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Biomedical subjects

P E McGregor

Publications and source records attributed to P E McGregor.

7 recordsLinked to original sources
PubMed1996

Ischemia-induced peripheral arterial vasospasm role of alpha 1- and alpha 2-adrenoceptors.

Ischemia produces functional and structural alterations in peripheral blood vessels. Our study was designed to investigate alpha-adrenoceptor modifications induced by prolonged ischemia and their role in enhancing the contractile response during reperfusion in canine femoral arteries. Unilateral vessel ischemia was created by double crossclamping a femoral artery and was maintained for 3 hr. Reperfusion was allowed for 1 hr. The contralateral femoral artery was utilized as a control. The vessels were harvested for contractile and binding studies. Isometric tension studies revealed that the magnitude of the maximum contractile response to norepinephrine (NE), potassium chloride (KCl), and methoxamine was 671 +/- 82 mg/mm2 versus 245 +/- 43 mg/mm2 (P < 0.01), 485 +/- 46 mg/mm2 versus 229 +/- 62 mg/mm2 (P < 0.05), and 486 +/- 88 mg/mm2 versus 126 +/- 38 mg/mm2 (P < 0.01), respectively for ischemic and nonischemic femoral arteries. EC50 values showed that ischemic vessels were more sensitive to NE, KCl, and methoxamine (P < 0.05). Sodium nitroprusside induced concentration-dependent and complete relaxation in all arterial rings (100% relaxation) but the ischemic femoral artery showed less sensitivity (P < 0.05). Binding studies showed that the number of binding sites (Bmax) for [3H]Prazosin and [3H]Rauwolscine were significantly increased in ischemic versus nonischemic vessels (1261 +/- 95 fmole/mg versus 704 +/- 113 fmole/mg, P < 0.03, and 490 +/- 86 fmole/mg versus 175 +/- 15 fmole/mg, P < 0.04, respectively). Furthermore, a significant decrease in affinity (Kd) for [3H]Prazosin and [3H]Rauwolscine was observed in ischemic versus nonischemic tissues (9.4 +/- 1.7 nM versus 4 +/- 0.2 nM, P < 0.02, and 6.4 +/- 1.5 nM versus 1.8 +/- 0.6 nM, P < 0.01, respectively). The increase in canine femoral artery vasoreactivity, following prolonged ischemia, seems to be also due to an increased density and functional activity of alpha-adrenoceptors expressed by the ischemic arterial smooth muscle cells.

Animals↗
PubMed1996

Modulation of monocyte adherence to endothelial cells by endothelin-1 involvement of Src (p60src) and JAK1-like kinases.

PURPOSE: The purpose of this study was to determine the transmembrane signaling pathway by which endothelin-1 (ET-1) enhances monocyte adherence to human umbilical vein endothelial cells (HUVECs) and to investigate the role of tyrosine kinases in this mechanism. METHODS: Adherence of purified human blood monocytes to HUVEC monolayers was assessed with radiolabeled monocytes. Tyrosine kinase activation was examined by immunoprecipitation and Western blotting. RESULTS: ET-1 potentiated monocyte adherence to HUVECs in a biphasic manner with peaks at 10(-10) mol/L and 10(-7) mol/L. A potent antagonist to ET B receptors, when used alone, had no effect. However, the antagonist, when combined with ET-1, significantly enhanced monocyte adherence to HUVECs. Incubation of ET-1 (10(-12) mol/L to 10(-7) mol/L) with HUVECs activated tyrosine kinases in a biphasic manner as identified by immunoblotting with PY20 antibody to tyrosine phosphorylated proteins. Phosphorylated proteins with Mr 60, 110, and 130 kDa were observed after ET-1 stimulation of HUVECs. Of interest, ET A or ET B receptor antagonists failed to antagonize the effect of ET-1. Rather, these receptor antagonists significantly augmented ET-1 induced tyrosine phosphorylation in HUVECs. Immunoprecipitation with antibodies to p60SRC and JAK1 kinases followed by immunoblotting with PY20 antibody suggested that ET-1 receptor response coupling in HUVECs involves the activation of p60SRC and JAK1-like kinases. CONCLUSIONS: These data suggest an association between activation of p60SRC and JAK1-like kinases and monocyte adherence in response to ET-1. ET-1-induced monocyte adherence is upregulated by ET B receptor antagonist, suggesting a negative feedback on cell adhesion through this receptor.

Blotting, Western↗
PubMed1995

Effect of endothelin-1 on arterial response to Bay K 8644. A comparison of ischemic and nonischemic arteries.

Endothelin-1 (ET-1) has been proposed as one of the possible mediators of the vasoconstriction seen following ischemia and reperfusion. We investigated the effect of ischemia and reperfusion on the contractile response of canine renal and iliac arteries to the dihydropyridine-type calcium channel agonist (+/-)Bay K 8644, following subthreshold doses of ET-1. No significant difference in the maximum tension was observed between the ischemic and nonischemic arteries in response to Bay K 8644 in the absence of ET-1. The addition of subthreshold dose of ET-1 (10(-10) M) resulted in a significant increase in sensitivity to Bay K 8644 in both the ischemic-reperfused and non-ischemic-reperfused arteries, with a 38 fold increase in iliac arteries and about 8 fold increase in the renal arteries. However, the ET-1 potentiated response was enhanced in the ischemic-reperfused in comparison to the non-ischemic-reperfused vessels in the iliac artery. These data suggest that the potentiating mechanism of ET-1 is not only intact, but enhanced in ischemic-reperfused vessels. Since the enhanced release of ET-1 in vivo is preceded by ischemia and reperfusion, the vasospastic phenomenon observed following these events could well be mediated by ET-1.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Attenuation of human leukocyte adherence to endothelial cell monolayers by tyrosine kinase inhibitors.

Expression of cell adhesion molecules is controlled by various cytokines including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha), but the underlying mechanisms are not clear. In this study, we investigated the role of tyrosine phosphorylated proteins in the regulation of leukocyte adhesion to endothelial cells. We examined the effect of genistein and herbimycin-A, selective inhibitors of tyrosine kinase, on the adherence of human blood neutrophils, lymphocytes, and monocytes to monolayers of human umbilical vein endothelial cells. Both genistein and herbimycin A significantly inhibited IL-1 and TNF alpha-induced upregulation of neutrophils (p < 0.05) and monocyte (p < 0.01) adherence. IL-1 and TNF alpha-stimulated lymphocyte adherence was diminished in the presence of herbimycin A (p < 0.05), but genistein only inhibited TNF alpha-stimulated adherence. There was no significant effect of genistein on IL-1-induced lymphocyte adherence. These novel findings reveal for the first time that tyrosine phosphorylated proteins may regulate leukocyte adherence and cell adhesion molecule expression on the endothelium.

Analysis of Variance↗
PubMed1994

Technique for assessment of leukocyte adherence to human umbilical vein endothelial cell monolayers.

The interaction between endothelial cells and immune/inflammatory cells plays an important role in the pathogenesis of vascular diseases. Inflammatory cells also activate endothelial cells and release both proliferative and cytotoxic mediators. In order to examine the interaction between leukocytes and endothelial cells and the effect of various drugs, we established the methodology for isolating and culturing the endothelial cells from human umbilical vein. Endothelial cells were harvested by using 0.1% collagenase within 48 hr of collecting the cord. Cells were grown to confluency in 96-well plates in Medium 199 containing 20% fetal calf serum, endothelial cell growth supplement, heparin, and antibiotics. Using this method, we obtained a confluent layer of the cells in all the 96 wells within 48 hr. We then examined the effect of peptides, endothelin-1, substance P, and neurokinin-A on the adherence of human blood neutrophils (purity and viability > 98%) to endothelial monolayers. All the peptides enhanced (p < 0.05) the adherence of neutrophils to endothelial cells in a time-dependent manner. This method of endothelial cell culturing is reliable, reproducible, and effective in evaluating the role of various mediators and drugs on the adherence of various white blood cells to endothelium.

Cell Adhesion↗
PubMed1993

Posttraumatic innominate artery aneurysm with occlusion of the common carotid artery at its origin by an intimal flap.

Blunt trauma involving the innominate and carotid arteries is a rare occurrence that can be lethal or have serious neurologic sequelae. To our knowledge this is the first reported case in the international literature describing the association of posttraumatic innominate artery aneurysm with total occlusion and thrombosis of the common carotid artery at its origin by an intimal flap. The diagnostic problems created by this unusual injury are discussed. In this case the patency of the distal portion of the common and internal carotid arteries was demonstrated by magnetic resonance angiography (MRA), whereas color duplex and digital arteriographic studies were unsuccessful. This demonstration was crucial to patient management. Since no studies are available comparing color duplex imaging, conventional arteriography, and MRA in the evaluation of blunt carotid trauma, this case study is presented to demonstrate the utility of MRA in emergency situations. In addition, we analyze the possible pathogenesis and discuss the surgical treatment.

Adolescent↗