Biomedical subjects

M T Nelson

Publications and source records attributed to M T Nelson.

At least 73 records · Page 4Linked to original sources

PubMed1996

Inward rectifier K+ currents in smooth muscle cells from rat coronary arteries: block by Mg2+, Ca2+, and Ba2+.

Inward rectifier K+ channels have been implicated in the control of membrane potential and external K(+)-induced dilations of small coronary arteries. To identify and characterize inward rectifier K+ currents in coronary artery smooth muscle, whole cell K+ currents in smooth muscle cells enzymatically isolated from rat coronary (septal) arteries (diameters, 100-150 microns) were measured in the conventional and perforated configurations of the patch-clamp technique. Ba(2+)-sensitive, whole cell K+ current-voltage relationships exhibited inward rectification. Blockers of Ca(2+)-activated K+ channels (1 mM tetraethylammonium ion), ATP-sensitive K+ channels (10 microM glibenclamide), and voltage-dependent K+ channels (1 mM 4-aminopyridine) in smooth muscle did not affect inward rectifier K+ currents. The nonselective K+ channel inhibitor phencyclidine (100 microM) reduced inward rectifier K+ currents by approximately 50%. External Ba2+ reduced inward currents, with membrane potential hyperpolarization increasing inhibition. The half-inhibition constant for Ba2+ was 2.1 microM at -60 mV, decreasing e-fold for a 25-mV hyperpolarization. External Cs+ also blocked inward rectifier K+ currents, with the half-inhibition constant for Cs+ of 2.9 mM at -60 mV. External Ca2+ and Mg2+ reduced inward rectifier K+ currents. At -60 mV, Ca2+ and Mg2+ (1 mM) reduced inward currents by 33 and 21%, respectively. Inward rectification was not affected by dialysis of the cell's interior with a nominally Ca(2+)- and Mg(2+)-free solution. These findings indicate that inward rectifier K+ channels exist in coronary artery smooth muscle and that Ba2+ may be a useful probe for the functional role of inward rectifier K+ channels in coronary arteries.

Animals↗

PubMed1996

ATP-sensitive potassium channels in cultured arterial segments.

Organ cultures of arteries have been used to study growth responses, proliferation, and contractility. However, the function of specific-ion channels in cultured arteries has not been investigated. ATP-sensitive K+ (KATP) channels play an important role in the control of arterial tone. The goal of this study was to determine the functional state of KATP channels in arteries kept in culture. Segments from rabbit mesenteric arteries were cultured in for 2-7 days. To explore the properties of KATP channels, the effects of KATP-channel modulators and other vasoactive substances on isometric force, density, and modulation of KATP currents in single smooth muscle cells isolated from cultured vessels were examined. Isometric contractions were measured with a resistance-vessel myograph. Whole cell KATP currents were recorded with the patch-clamp technique. Membrane capacitance and KATP-current density in single smooth muscle cells from freshly dissected (control) and cultured arteries were not altered. At -60 mV, glibenclamide-sensitive currents in the presence of the K(+)-channel opener pinacidil were -4.7 +/- 1.2, -4.7 +/- 0.6, and -4.6 +/- 0.7 pA/pF for control and 2- and 4-day arteries, respectively. Inhibitory modulation of KATP currents in arterial smooth muscle also remained intact for 4 days in culture; the vasoconstrictor histamine (10 microM) reduced glibenclamide-sensitive currents in the presence of pinacidil by 61.2 +/- 2.8, 42.4 +/- 10.1, and 41.2 +/- 6.1% for control and 2- and 4-day arteries, respectively. Pinacidil relaxed control and cultured arteries (1-7 days) in a dose-dependent manner. Half-maximal effective concentrations of pinacidil were 0.42, 0.24, 0.23, and 0.51 microM for control and 2-, 4-, and 7-day arteries, respectively, whereas maximal relaxations to pinacidil were 62.9, 47.5, 37.5, and 55.7% for control and 2-, 5-, and 7-day arteries, respectively. Histamine, norepinephrine, and serotonin constricted cultured arteries, although responses to histamine and norepinephrine diminished by 30-50% after 5 days in culture. The relaxant effect of acetylcholine was not maintained in cultured arteries. Sodium nitroprusside, however, effectively relaxed arteries cultured for 2-7 days. The data indicate that with the culture model described, KATP channels in arterial smooth muscle remained functional and contractile responses in arterial segments were maintained for up to 7 days. These results suggest that this approach can be used to study either long-term regulation of KATP channels or the role of this channel type in growth responses.

Acetylcholine↗

PubMed1996

Zeneca ZD6169 activates ATP-sensitive K+ channels in the urinary bladder of the guinea pig.

The effects of Zeneca ZD6169, a tertiary carbinol, and levcromakalim were examined on the membrane potential of intact smooth muscle cells, and on ATP-sensitive K+ (KATP) channel currents in isolated smooth muscle cells from the guinea pig urinary bladder. ZD6169 and levcromakalim induced a glibenclamide-sensitive hyperpolarization of the membrane potential. The ZD6169- and levcromakalim-induced KATP currents were half-maximal at 1.02 and 2.63 mumol/l, respectively, with Hill coefficients of 1.46 and 1.62, respectively. The ZD6169-induced KATP currents were inhibited by internal ATP (3.0 mmol/l), reduced 34% by activators of protein kinase C, and decreased 35% when the external pH was lowered to 6.4. This study provides the first characterization of ZD6169 on KATP currents and indicates that ZD6169 is a potent opener of KATP channels in the smooth muscle from the urinary bladder.

Adenosine Triphosphate↗

PubMed1996

Gender differences in coronary artery diameter involve estrogen, nitric oxide, and Ca(2+)-dependent K+ channels.

During their reproductive years, women have a much lower incidence of coronary heart disease compared with men of similar age. Estrogen appears to be largely responsible for this decrease in cardiovascular mortality in women. In the present study, isolated pressurized coronary arteries from rats were used to assess the role of gender and circulating estrogen on coronary vascular function. Pressure-induced constrictions ("myogenic tone") were greater (approximately 2-fold) in isolated coronary arteries from estrogen-deficient male or ovariectomized (OVX) rats compared with similar arteries obtained from female rats or OVX rats receiving physiological levels of estrogen replacement (OVX+E group). These differences in coronary artery diameter were abolished by removal of the vascular endothelium or chemical inhibition of NO synthase. The anti-estrogen, tamoxifen, increased pressure-induced constrictions of coronary arteries from female and OVX+E rats. Dilations of pressurized coronary arteries from female and OVX animals to sodium nitroprusside, a nitrovasodilator that generates NO, were reduced by > 50% by iberiotoxin (IBTX), an inhibitor of Ca(2+)-dependent K+ (KCa) channels. Sodium nitroprusside (10 mumol/L) hyperpolarized coronary arteries by 13 +/- 2 mV, an effect that was greatly diminished (approximately 80%) by IBTX. Coronary arteries isolated from female rats produced greater constrictions in response to IBTX and KT 5823, an inhibitor of cGMP-dependent protein kinase, compared with coronary arteries from OVX rats. cGMP-dependent protein kinase increased the activity of KCa channels 16.5 +/- 5-fold in excised membrane patches from smooth muscle cells enzymatically isolated from these small coronary arteries. We propose that physiological levels of circulating 17 beta-estradiol elevate basal NO release from the endothelial cells, which increases the diameter of pressurized coronary arteries. Further, our results suggest that part of the effect of this NO is through activation of KCa channels in the smooth muscle cells of the coronary arteries.

Animals↗

PubMed1996

Studies of the K(ATP) channel opening activity of the new dihydropyridine compound 9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridined ione in bladder detrusor in vitro.

The potassium (K+) channel opening activity of ZM244085 (9-(3-cyanophenyl)-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-acridined ione, CAS 149398-59-4), a novel dihydropyridine (DHP), was ascertained. In a set of functional assays, its mechanoinhibitory effect on myogenic activity of guinea pig bladder detrusor muscles, either mildly or highly depolarized with 15 or 80 mmol/l KCl, was measured. ZM244085 had negligible effect on the tone of the detrusor contracted with 80 mmol/l KCl but reduced the myogenic activity induced with 15 mmol/l KCl (IC50=4.2 +/- 0.4 mumol/l). Glibenclamide, an ATP-sensitive K+ (KATP) channel blocker, competitively antagonized this action of ZM244085 with a pA2 value of 7.6. This functional profile of ZM244085 is similar to that of the prototypic K+ channel opener cromakalim but stands in contrast to that of typical DHP Ca2+ channel blockers such as nifedipine and nimodipine. The membrane potential of the guinea pig detrusor, recorded with intracellular microelectrodes, was hyperpolarized 6.8 +/- 3.1 mV by ZM244085 (10 mumol/l). This hyperpolarization was completely blocked by glibenclamide but not affected by apamin (10 mumol/l), a toxin blocking specifically small conductance and Ca2+ dependent K+ (SKCa) channels. ZM244085 (10 mumol/l) increased the whole cell KATP current in isolated guinea pig detrusor cells by 8.8 +/- 2.5 pA, but failed to activate large conductance and Ca2+ dependent K+ (BKCa) channels in excised inside-out membrane patches from those cells. The results from these studies showed that ZM244085 is a K+ channel opener which activates predominantly KATP channels in vitro to relax bladder detrusors.

Acridines↗

PubMed1996

Intrapancreatic cholecystokinin mediates vagally stimulated exocrine secretion from the rat pancreas.

Although cholecystokinin is localized within neuronal fibres of the pancreas, a physiological role for intrapancreatic cholecystokinin has not been identified. The strategy of this study was to elicit pure vagal stimulation electrically, and to use specific receptor antagonists to identify the mediators of exocrine pancreatic secretion. We conclude that vagal stimulation of the rat pancreas involves ganglionic neurotransmission and release of acetylcholine and cholecystokinin from intrapancreatic, postganglionic fibres. To our knowledge, this is the first study to demonstrate a physiological role for intrapancreatic cholecystokinin.

Animals↗

PubMed1996

Study on inhibition of pancreatic exocrine secretion by somatostatin in rats.

We used a potent and specific monoclonal antibody to somatostatin to test the physiologic inhibitory role of the tetradecapeptide somatostatin on pancreatic secretion. Somatostatin immunoneutralization increased both the total amylase and volume of pancreatic secretion. Cholecystokinin-A receptor antagonism abolished the stimulatory effect of somatostatin immunoneutralization. We conclude that somatostatin tonically inhibits, pancreatic secretion in fasted rats via inhibition of the release or action of cholecystokinin. Furthermore, the source of these peptides is likely islet delta cells and intrapancreatic neurons, respectively.

Amylases↗

PubMed1996

Rat exocrine pancreatic secretion by vagal stimulation occurs via multiple mediators.

The vagus is a mixed nerve containing cholinerrgic and non-cholinergic neurons. Vagal fibers interact with peptidergic neurons of the enteric nervous system which stain immunohistochemically for cholecystokinin, vasoactive intestinal polypeptide, and gastrin releasing peptide. The contribution of these peptidergic neurons in the pancreatic response to vagal stimulation is unknown. We tested the effect of specific inhibitor of these stimulants against vagally mediated exocrine secretion in rats. The response to vagal stimulation was blocked significantly by each of the following: the ganglionic blocker hexamethonium (100% inhibition); the muscarinic, cholinergic blocker atropine (85% inhibition); the specific cholecystokinin-A receptor blocker (91% inhibition); and a vasoactive intestinal polypeptide polyclonal antibody (89% inhibition). This observation is consistent with the hypothesis that potentiating interactions among several agonists mediate the vagal response. Our study, however, dose not exclude acetylcholine as the final common mediator.

Amylases↗

PubMed1995

Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptors and cAMP-dependent protein kinase.

The mechanism by which the endogenous vasodilator adenosine causes ATP-sensitive potassium (KATP) channels in arterial smooth muscle to open was investigated by the whole-cell patch-clamp technique. Adenosine induced voltage-independent, potassium-selective currents, which were inhibited by glibenclamide, a blocker of KATP currents. Glibenclamide-sensitive currents were also activated by the selective adenosine A2-receptor agonist 2-p-(2-carboxethyl)-phenethylamino-5'-N- ethylcarboxamidoadenosine hydrochloride (CGS-21680), whereas 2-chloro-N6-cyclopentyladenosine (CCPA), a selective adenosine A1-receptor agonist, failed to induce potassium currents. Glibenclamide-sensitive currents induced by adenosine and CGS-21680 were largely reduced by blockers of the cAMP-dependent protein kinase (Rp-cAMP[S], H-89, protein kinase A inhibitor peptide). Therefore, we conclude that adenosine can activate KATP currents in arterial smooth muscle through the following pathway: (i) Adenosine stimulates A2 receptors, which activates adenylyl cyclase; (ii) the resulting increase intracellular cAMP stimulates protein kinase A, which, probably through a phosphorylation step, opens KATP channels.

Adenosine↗

PubMed1995

Relaxation of arterial smooth muscle by calcium sparks.

Local increases in intracellular calcium ion concentration ([Ca2+]i) resulting from activation of the ryanodine-sensitive calcium-release channel in the sarcoplasmic reticulum (SR) of smooth muscle cause arterial dilation. Ryanodine-sensitive, spontaneous local increases in [Ca2+]i (Ca2+ sparks) from the SR were observed just under the surface membrane of single smooth muscle cells from myogenic cerebral arteries. Ryanodine and thapsigargin inhibited Ca2+ sparks and Ca(2+)-dependent potassium (KCa) currents, suggesting that Ca2+ sparks activate KCa channels. Furthermore, KCa channels activated by Ca2+ sparks appeared to hyperpolarize and dilate pressurized myogenic arteries because ryanodine and thapsigargin depolarized and constricted these arteries to an extent similar to that produced by blockers of KCa channels. Ca2+ sparks indirectly cause vasodilation through activation of KCa channels, but have little direct effect on spatially averaged [Ca2+]i, which regulates contraction.

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

PubMed1995

Physiological roles and properties of potassium channels in arterial smooth muscle.

This review examines the properties and roles of the four types of K+ channels that have been identified in the cell membrane of arterial smooth muscle cells. 1) Voltage-dependent K+ (KV) channels increase their activity with membrane depolarization and are important regulators of smooth muscle membrane potential in response to depolarizing stimuli. 2) Ca(2+)-activated K+ (KCa) channels respond to changes in intracellular Ca2+ to regulate membrane potential and play an important role in the control of myogenic tone in small arteries. 3) Inward rectifier K+ (KIR) channels regulate membrane potential in smooth muscle cells from several types of resistance arteries and may be responsible for external K(+)-induced dilations. 4) ATP-sensitive K+ (KATP) channels respond to changes in cellular metabolism and are targets of a variety of vasodilating stimuli. The main conclusions of this review are: 1) regulation of arterial smooth muscle membrane potential through activation or inhibition of K+ channel activity provides an important mechanism to dilate or constrict arteries; 2) KV, KCa, KIR, and KATP channels serve unique functions in the regulation of arterial smooth muscle membrane potential; and 3) K+ channels integrate a variety of vasoactive signals to dilate or constrict arteries through regulation of the membrane potential in arterial smooth muscle.

Animals↗

PubMed1995

Pharmacology of ATP-sensitive K+ currents in smooth muscle cells from rabbit mesenteric artery.

The inference that ATP-sensitive K+ (KATP) channels are involved in arterial responses to the synthetic K+ channel openers, hypoxia, adenosine, and calcitonin gene-related peptide, has relied on the sensitivity of these responses to the sulfonylureas glibenclamide and tolbutamide and to tetraethylammonium (TEA+). The inhibition of KATP currents by glibenclamide, tolbutamide, and TEA+ was investigated in single smooth muscle cells from rabbit mesenteric artery by use of the whole cell patch-clamp technique. The synthetic K+ channel openers pinacidil (half-activation 0.6 microM), cromakalim (half-activation 1.9 microM), and diazoxide (half-activation 37.1 microM) activated K(+)-selective currents that were blocked by glibenclamide. Elevation of pipette (intracellular) ATP concentration decreased K+ currents induced by pinacidil. Half-inhibition of KATP currents by glibenclamide and tolbutamide occurred at 101 nM and 351 microM, respectively. KATP currents were also inhibited by external TEA+, with half-inhibition at 6.2 mM. The results indicate that glibenclamide is an effective inhibitor of KATP channels in arterial smooth muscle and that tolbutamide and TEA+ are much less effective. Furthermore, these results support numerous functional studies that have demonstrated that the vasorelaxations to K+ channel openers are inhibited by < 10 microM glibenclamide but not by < 1 mM TEA+.

Adenosine Triphosphate↗

PubMed1995

Regulation of membrane potential and diameter by voltage-dependent K+ channels in rabbit myogenic cerebral arteries.

The hypothesis that voltage-dependent K+ channels are involved in the regulation of arterial smooth muscle membrane potential and blood vessel diameter was tested by examining the effects of inhibitors [4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP)] of voltage-dependent K+ channels on the membrane potential and diameter of pressurized small (100- to 300-microns diam) cerebral arteries from rabbit. In response to graded elevations in transmural pressure (20-100 mmHg), the membrane potential of smooth muscle cells in these arteries depolarized and the arteries constricted. 4-AP (1 mM) and 3,4-DAP (1 mM) depolarized cerebral arteries by 19 and 21 mV, respectively, when they were subjected to a transmural pressure of 80 mmHg. 3-Aminopyridine (3-AP, 1 mM), which is a relatively poor inhibitor of voltage-dependent K+ channels, depolarized smooth muscle cells in the arteries by 1 mV. 4-AP and 3,4-DAP constricted pressurized (to 80 mmHg) cerebral arteries. 3-AP had little effect on arterial diameter. 4-AP increased the arterial constriction to transmural pressure over a wide range of pressures (40-90 mmHg). The effects of 4-AP and 3,4-DAP on membrane potential and diameter were not prevented by inhibitors of calcium channels, calcium-activated K+ channels, ATP-sensitive K+ channels, inward rectifier K+ channels, blockers of adrenergic, serotonergic, muscarinic, and histaminergic receptors, or removal of the endothelium. These results suggest that voltage-dependent K+ channels are involved in the regulation of membrane potential and response of small cerebral arteries to changes in intravascular pressure.

4-Aminopyridine↗

PubMed1995

ATP-sensitive K+ currents in cerebral arterial smooth muscle: pharmacological and hormonal modulation.

Calcitonin gene-related peptide (CGRP), hypoxia, and synthetic activators of ATP-sensitive potassium (KATP) channels (e.g., pinacidil and levcromakalim) cause dilation of cerebral arteries that are attenuated by the KATP channel inhibitor glibenclamide. We have identified and characterized KATP currents in smooth muscle cells isolated from rabbit cerebral arteries, using the whole cell configuration of the patch-clamp technique. Pinacidil (10 microM) and levcromakalim (10 microM) increased glibenclamide-sensitive currents about sixfold in cells dialyzed with 0.1 mM ATP. Glibenclamide-sensitive currents in the presence of pinacidil were potassium selective, voltage independent, and reduced about threefold by elevating intracellular ATP from 0.1 to 3.0 mM. External tetraethylammonium and 4-aminopyridine at millimolar concentrations reduced pinacidil-induced currents, whereas iberiotoxin, a blocker of calcium-activated potassium channels, had no effect. The vasoconstrictors serotonin and histamine also inhibited pinacidil-induced currents. The vasodilators CGRP and adenosine, in contrast, increased glibenclamide-sensitive potassium currents. We conclude that cerebral artery smooth muscle cells have KATP channels that are regulated by endogenous vasoconstrictors and vasodilators. We propose that these channels are involved in the dilation of cerebral arteries to CGRP and synthetic vasodilators.

4-Aminopyridine↗

PubMed1994

Activation of ATP-sensitive potassium currents in guinea-pig gall-bladder smooth muscle by the neuropeptide CGRP.

1. The actions of a neuroactive peptide, calcitonin gene-related peptide (CGRP), and the ATP-sensitive potassium (K+ATP) channel activator lemakalim on guinea-pig gall-bladder smooth muscle cells were investigated using intracellular recording from intact preparations and whole-cell patch clamp recording from acutely dissociated myocytes. 2. CGRP and lemakalim caused a glibenclamide-sensitive hyperpolarization of the plasma membrane of intact cells with an associated suppression of spontaneous action potentials. 3. In isolated smooth muscle cells, CGRP (10 nM) and lemakalim (10 microM) activated currents that were glibenclamide sensitive, voltage independent and potassium selective. 4. External TEA+ at 1.0 and 10.0 mM inhibited glibenclamide-sensitive, CGRP-activated currents by 3.8 and 66.5%, respectively. 5. Increases in the intracellular ATP concentration from 0.1 to 5.0 mM reduced the glibenclamide-sensitive potassium current in the presence of CGRP (10 nM) or lemakalim (10 microM) by > 60%. The increase in the intracellular ATP also reduced the steady-state glibenclamide-sensitive current by > 80%. 6. These findings indicate that CGRP activates K+ATP channels to hyperpolarize the membrane of gall-bladder smooth muscle cells. This hyperpolarization may be an important mechanism underlying the relaxant effects of CGRP on the gall-bladder.

Adenosine Triphosphate↗

PubMed1994

Calcitonin gene-related peptide activated ATP-sensitive K+ currents in rabbit arterial smooth muscle via protein kinase A.

1. Whole-cell K+ currents activated by calcitonin gene-related peptide (CGRP) in smooth muscle cells enzymatically isolated from rabbit mesenteric arteries were measured in the conventional and perforated configurations of the patch clamp technique. The signal transduction pathway from CGRP receptors to activation of potassium currents was investigated. 2. CGRP (10 nM) activated a whole-cell current that was blocked by glibenclamide (10 microM), an inhibitor of ATP-sensitive K+ channels. Elevating intracellular ATP reduced glibenclamide-sensitive currents. CGRP increased the glibenclamide-sensitive currents by 3- to 6-fold in cells dialysed with 0.1 mM ATP, 3.0 mM ATP or in intact cells. The reversal potential of the glibenclamide-sensitive current in the presence of CGRP shifted with the potassium equilibrium potential, while its current-voltage relationship exhibited little voltage dependence. 3. Forskolin (10 microM), an adenylyl cyclase activator, Sp-cAMPS (500 microM) and the catalytic subunit of protein kinase A increased glibenclamide-sensitive K+ currents 2.1-, 3.3- and 8.2-fold, respectively. 4. Nitric oxide and nitroprusside did not activate glibenclamide-sensitive K+ currents. 5. Dialysis of the cell's interior with inhibitors of protein kinase A (synthetic peptide inhibitor, 4.6 microM or H-8, 100 microM) completely blocked activation of K+ currents by CGRP. 6. Our results suggest the following signal transduction scheme for activation of K+ currents by CGRP in arterial smooth muscle: (1) CGRP stimulates adenylyl cyclase, which leads to an elevation of cAMP; (2) cAMP activates protein kinase A, which opens ATP-sensitive K+ channels.

Adenosine Triphosphate↗

PubMed1994

Noninvasive method for the detection of bowel ischemia: computed tomography detection of absorbed iodinated contrast material.

RATIONALE AND OBJECTIVES: Although systemic absorption of enterically administered iohexol and its excretion in urine has been previously documented in rats with ischemic bowel, a practical and sensitive method of detecting urinary iohexol has not been available. We proposed to detect the presence of iohexol in the urine of rats with normal and ischemic bowel by use of a computed tomography (CT) number increase in the bladder with the use of CT. METHODS: Anesthetized rats (250 g) underwent either sham laparotomy (n = 6), ligation of two vascular arcades to the proximal jejunum (n = 5), ligation of six vascular arcades to the proximal jejunum (n = 6), or ligation of the superior mesenteric artery (n = 6). Rats were hydrated with saline (3.2 ml/hr intravenously). Each received a 3-ml enteric bolus of isotonic iohexol. Serial CT scans and plain film radiographs of the bladder were performed at 2, 4, and 6 hr to detect systemic absorption of contrast from the gut. Urine iohexol concentrations were measured by capillary electrophoresis. CT number and iohexol concentration were compared with evidence from plain film radiographs of bladder opacification. Intestinal ischemia was graded histologically. RESULTS: Histologic evidence of ischemia was present in all six-arcade and five of six superior mesenteric artery (SMA)-ligated animals. No animals in the control or two-arcade group showed evidence of bowel ischemia. Statistically significant increases (P < 0.05) in bladder density were demonstrated in the six-arcade and SMA-ligated groups. No statistical difference was noted between the two-arcade ligation and control groups. CONCLUSIONS: Experimental intestinal ischemia was reliably detected by bladder opacification after administration of enteric contrast. CT detection of systemic absorption of enteric iohexol was more sensitive than plain film radiographs and may be useful in the diagnosis of intestinal ischemia, although it may not be specific for ischemia.

Animals↗

PubMed1994

The role of the membrane potential of endothelial and smooth muscle cells in the regulation of coronary blood flow.

In the mammalian heart the supply of oxygen and energy-rich substrates through the coronary arterioles is continuously adapted to the variations of cardiac work. The coronary resistance arteries and the surrounding myocardium form a functional unit with multiple interactions between coronary endothelial cells, smooth muscle cells, perivascular nerves, and cardiac muscle cells. We describe the mechanisms underlying the electrical and chemical communication between the different cell types, the ionic channels contributing to the resting potential of endothelial and smooth muscle cells, and the mechanisms responsible for modulation of the resting potential. The main conclusion of our analysis is that the membrane potential of coronary endothelial and smooth muscle cells is one of the major determinants of coronary blood flow, and that modulation of the membrane potential provides a way to dilate or constrict coronary resistance arteries. It is proposed that the membrane potential of the myo-endothelial regulatory unit, i.e., of the endothelial cells and the underlying smooth muscle cells in the terminal arterioles, may function as an integrator of the numerous local and global vasodilator and constrictor signals that provide for the adaptation of coronary blood flow to the metabolic demands of the heart.

Animals↗