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D C Crossman

Publications and source records attributed to D C Crossman.

43 records · Page 3Linked to original sources
PubMed1990

Differential regulation by cytokines of constitutive and stimulated secretion of von Willebrand factor from endothelial cells.

We examined the effect of cytokines on basal and agonist-stimulated release of von Willebrand factor (vWf) by human endothelial cells. Treatment of endothelial cells for up to 48 hours with human recombinant or purified interleukin 1 (IL-1) or human recombinant tumor necrosis factor-alpha (TNF-alpha) did not significantly affect constitutive secretion of vWf or intracellular levels of vWf, although basal prostacyclin (PGI2) production was markedly enhanced. In contrast, both IL-1 and TNF-alpha modulated vWf release in response to thrombin or phorbol ester. Pretreatment of endothelial cells for 2 hours with either cytokine enhanced by up to threefold the stimulatory effect of a subsequent 60-minute exposure to thrombin. Addition of cycloheximide (5 micrograms/mL) during the preincubation abolished this enhancement. Moreover, if the cytokine pretreatment time was extended to 24 hours, agonist-stimulated vWf release was significantly suppressed. Cytokine treatment for 2 or 24 hours had no detectable effect on levels of vWf messenger RNA. The effects of cytokines were not the result of contamination with bacterial lipopolysaccharide and were not attributable to endothelial cell injury. These results show that cytokines have little or no direct effect on vWf release from endothelial cells but can significantly modulate its acute release in response to other stimuli in a complex time- and dose-dependent manner.

Blotting, Northern↗
PubMed1990

Action of calcitonin gene-related peptide upon bovine vascular endothelial and smooth muscle cells grown in isolation and co-culture.

1. Bovine aortic endothelial cells (BAE) and smooth muscle cells (BASM) were grown separately and in co-culture. 2. Calcitonin gene-related peptide (CGRP) caused dose-dependent activation of adenylate cyclase in each cell type when grown in isolation. The concentration of CGRP causing half-maximal activation in BAE and BASM was 200 nM and 310 nM, respectively. 3. In cells grown in co-culture exposure to bradykinin produced dose-dependent elevations in cyclic GMP content which were maximal 1 min after application of the agonist. 4. CGRP (1 nM-1 microM) did not stimulate a rise in cyclic GMP in co-cultures. 5. Displaceable CGRP binding was identified throughout the wall of the bovine aorta. 6. We conclude that CGRP receptors coupled to adenylate cyclase are present on BAE and BASM, but there is no coupling of these receptors to the release of any agent (such as endothelium-derived relaxing factor) that activates guanylate cyclase.

Adenylyl Cyclases↗
PubMed1989

Substance P dilates epicardial coronary arteries and increases coronary blood flow in humans.

The effects of intracoronary infusions of substance P in conscious humans on epicardial vessel diameter and coronary sinus oxygen saturation were investigated in 13 patients who had angiographically normal coronary arteries. The dose of substance P ranged from 2.8 to 89.6 pmol/min, starting at 2.8 pmol/min and rising by doubling increments. All infusions were performed for 2-minute periods. Epicardial vessel diameter was measured by a computerized analysis system (CAAS) of the angiogram performed at the end of each infusion period. Coronary sinus oxygen saturation (CSO2) was measured continuously by a fiber-optic oximeter catheter in the coronary sinus. A reduction of arterial pressure, indicative of a systemic effect of substance P, occurred only when infusions were 44.8 pmol/min or more. At considerably smaller dosages, a dose-dependent increase in the left anterior descending artery diameter was seen with substance P; maximal dilation occurred at a dosage of 11.2 pmol/min. The percent increase in vessel diameter for this dosage was 29.4 +/- 19.8% (mean +/- SD) at the distal site of analysis and 16.7 +/- 10% at the proximal site of analysis. CSO2 rose in a dose-dependent manner and was maximal at a dosage of 11.2 pmol/min, which caused a 14.6 +/- 7.2% O2 rise above the preinfusion saturation of 43.5 +/- 11.1% O2. As the heart rate-blood pressure double product showed no change, it is argued that these changes in CSO2 probably reflect rises in coronary flow that were seen with dosages of substance P without systemic effect. In three patients, preconstriction induced by ergonovine was reversed by substance P infusions, which produced a degree of dilation equivalent to that of isosorbide dinitrate. We conclude that substance P at very small dosages, which are without peripheral effects, causes in vivo epicardial coronary artery dilatation as well as resistive vessel dilatation in humans.

Adult↗
PubMed1989

Endothelin-1: demonstration of potent effects on the microcirculation of humans and other species.

The effect of endothelin-1 (ET-1) on microvessels was investigated by use of intravital microscopy and by measuring microvascular blood flow changes. ET-1 caused a selective constriction of arterioles in the hamster cheek pouch, without affecting venules. A decrease in blood flow was observed at the site of intradermal injection of ET-1 in rabbit and human skin. ET-1, as a consequence of its vasoconstrictor activity, acted in an anti-inflammatory manner to inhibit edema formation and neutrophil accumulation induced by chemotactic agents in rabbit skin. In human skin, a flare, due to increased blood flow, spread for several centimeters around a central constricted area. The flare, the result of an axon reflex, reveals an alternative mechanism through which ET-1 can act to modulate vascular tone.

Animals↗
PubMed1988

Bradykinin induced wheal and flare is not mediated by histamine release or cyclooxygenase products.

The wheal and flare response to intradermal bradykinin was studied in man. The possibility that histamine and cyclooxygenase products are involved in the response to bradykinin was examined. Terfenadine given by mouth significantly inhibited the cutaneous response to histamine but the effect of bradykinin was unaltered. Similarly the cutaneous response to bradykinin was unchanged by aspirin.

Adult↗
PubMed1987

Sensory neuropeptide effects in human skin.

1 Neuropeptides released from sensory nerves may account for cutaneous flare and wheal following local trauma. In 28 normal subjects we have studied the effects of four sensory neuropeptides given by intradermal injection on the forearm or back. 2 All peptides caused a flare distant from the site of injection, presumably due to an axon reflex. Substance P (SP) was the most potent (geometric mean dose causing 50% of maximum flare, 4.2 pmol). Neurokinin A (NKA) was the next most potent with neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) the least. The distant flare response to SP, NKA and NKB was maximal at 5 min and disappeared within 2 h. 3 CGRP caused a local erythema over the site of injection at doses above 0.5 pmol which at higher doses lasted for up to 12 h. 4 SP, NKA and NKB caused wheals at doses above 5 pmol with SP and NKB being the most potent. CGRP (up to 250 pmol) did not consistently cause wheal formation. There was no significant effect of coinjection of CGRP upon the response to SP although there was a tendency for an enhancement of the wheal response. 5 The H1-histamine antagonist terfenadine (60 mg orally) significantly inhibited the wheal and distant flare response to histamine (5 nmol) and NKA, but not that caused by NKB. The distant flare of CGRP was also reduced but the local erythema was unaltered. 6. Aspirin (600 mg orally) significantly inhibited the distant flare response to SP, NKA and CGRP, but not that caused by NKB or histamine; the local erythema induced by CGRP was unaffected by aspirin. Aspirin also inhibited the wheal formed by NKA but not the wheal induced by the other substances. 7. These results suggest that tachykinins cause a distant flare response partially via the release of histamine and cyclo-oxygenase products, but cause a wheal by a direct effect on the skin microvasculature. The order of potency SP > NKB > NKA suggests that an SPp or NK, receptor is involved in the wheal response. CGRP by contrast has a direct vasodilator effect which is very prolonged.

Adult↗