Biomedical subjects

K G Proctor

Publications and source records attributed to K G Proctor.

At least 55 records · Page 3Linked to original sources

PubMed1991

Activation of brain adenosine receptors evokes vasodilation in skin arterioles.

Metabolically stable adenosine (ADO) agonists were infused into cannulas chronically implanted in the lateral cerebral ventricle intracerebroventricularly (icv) while responses in skin microcirculation of pentobarbital-anesthetized hamsters were observed with intravital microscopy. Cyclohexyladenosine (CHA; A1-receptor selective; 0.0001-1 pmol) and N-ethylcarboxoamidoadenosine (NECA; A2-receptor selective; 0.01-0.05 pmol) were delivered in 10 microliters of bicarbonate-buffered Ringer vehicle. Mean systemic arterial blood pressure, heart rate, skin arteriolar diameter, and red blood cell velocity were continuously monitored. Blood flow was calculated from measurements of arteriolar diameter (20-40 microns) and red blood cell velocity. CHA icv caused dose-related decreases in blood pressure and heart rate, as well as increases in cutaneous perfusion. Comparable amounts of CHA administered intravenously evoked no response. Pretreatment with an A1-selective antagonist xanthine amine congener (XAC, 5 pmol icv or 1 mg/kg iv) had no effect on the depressor response but antagonized the bradycardia. In contrast, a nonselective antagonist 8-phenyltheophylline (8pTHEO, 5 pmol icv or 0.3 mg/kg iv) had no effect on the bradycardia but attenuated the depressor response. By either route, both antagonists prevented the cutaneous microcirculatory responses evoked by icv CHA. NECA icv produced hypotension but no change in the skin, and the depressor response was not altered by icv XAC. These observations provide direct evidence that chemical stimulation of central nervous system (CNS) ADO receptors is linked to a cutaneous vascular response that can be dissociated from other cardiorespiratory depressant actions of CNS ADO.

Adenosine↗

PubMed1991

Direct vasoconstriction evoked by A1-adenosine receptor stimulation in the cutaneous microcirculation.

To determine whether the vasoconstriction evoked by A1-adenosine receptor stimulation in the skin circulation caused the release of other substances or whether A1 stimulation modulated the vasoconstriction evoked by other compounds, a potent A1-selective, synthetic agonist, cyclohexyladenosine (CHA), was topically applied simultaneously with several different vasoconstrictor agonists or antagonists. CHA was chosen instead of adenosine because the parent compound is metabolized quickly and also does not discriminate between A1 or A2 receptors. Blood flow was calculated from measurements of arteriolar diameter (40-60 microns) and red blood cell velocity using intravital videomicroscopy. Responses were recorded only in a steady state. The dose-related vasoconstriction evoked by CHA (ED50, 2.07 +/- 0.80 nM; half-minimal response, 93 +/- 1%) was not attenuated by antagonists to norepinephrine (phentolamine [11 microM] or prazosin [10 microM]), serotonin (methysergide [11 microM]), angiotensin II (saralasin [0.11 microM]), thromboxane (SK&F 88046 [13 microM]), or leukotrienes (SK&F 102922 [2.1 microM]). The vasoconstriction evoked by 2 nM CHA was attenuated by a subthreshold concentration (1 nM) of norepinephrine, whereas the vasoconstriction evoked by 0.1-1 microM norepinephrine was attenuated by a threshold concentration (1 nM) of CHA. Higher concentrations (10-100 nM) of CHA had no additional inhibitory effect. In contrast, CHA had no effect on the vasoconstrictions evoked by angiotensin II (10 nM or 1 microM) or serotonin (100 or 500 nM). Therefore, it is unlikely that A1-receptor stimulation causes the release of norepinephrine, serotonin, angiotensin, thromboxane, or leukotrienes in the skin microcirculation. Because norepinephrine attenuated the vasoconstriction evoked by CHA while CHA attenuated that evoked by norepinephrine, there appears to be a negative interaction between alpha-adrenergic and A1-adenosinergic receptors.

Adenosine↗

PubMed1991

Potentiation of leukotriene B4-mediated inflammatory response by the adenosine antagonist, 8-phenyl theophylline.

Previous in vitro studies have shown that adenosine (ADO)-induced inhibition of granulocyte function is near maximal at the sub-micromolar concentrations that would be anticipated in normal tissues. If this mechanism is operative in vivo, then antagonizing ADO receptors should potentiate granulocyte-mediated inflammatory responses. To unmask the putative inhibition, the antagonist, 8-phenyl theophylline (8pTHEO), was continuously suffused over the hamster cheek pouch microcirculation, which was observed with intravital bright field and fluorescence microscopy. As an index of inflammation, macromolecular permeability was measured by determining extravasation of fluorescein isothiocyanate-labelled dextran (MW 150,000). In addition, tissue specimens were fixed and stained with hematoxylin and eosin for histological quantification of intravascular and extravascular granulocytes. The tissue was challenged with a 10-40 min topical application of leukotriene B4 (LTB4, 1.1-4nM) or histamine (0.5 or 10 microM) with and without 8pTHEO, at a concentration (8 microM) that attenuated vasodilation evoked by exogenous ADO. These two inflammatory stimuli were chosen because LTB4 evokes a granulocyte-dependent response in the cheek pouch, while histamine evokes a granulocyte-independent response. 8pTHEO potentiated the dose-related increase caused by LTB4 but had no effect on permeability in baseline conditions or on the response evoked by histamine. In baseline conditions, there were fewer than 500 intravascular granulocytes/mm2 microvessel surface area and fewer than 3000 extravascular granulocytes/cm2 tissue surface area. After LTB4 challenge, there was a 3-4 fold increase in the numbers of extra- and intra-vascular granulocytes compared to baseline, but no dose-related relationship could be detected over the concentration range 1.1-4 nM. With 8pTHEO + 1.1 nM LTB4, the granulocyte accumulation was similar to that with LTB4 alone, but there were significantly more intravascular and extravascular granulocytes in the 8pTHEO after 2.5-4 nM LTB4. In context with previous studies, these results suggest that endogenous ADO exerts a tonic inhibitory influence on granulocytes during LTB4 stimulation and this action can be unmasked with methylxanthines.

Animals↗

PubMed1991

Beneficial actions of exogenous hyaluronic acid on wound healing.

To determine the effect of exogenous hyaluronic acid (HA) on healing of experimental wounds, responses in the hamster cheek pouch were measured after a hole was cut through the tissue with a biopsy punch. Fluorescence-labeled dextran was administered intravenously as a macromolecular tracer and the microcirculation was observed in vivo with a fluorescence microscope connected to a high-resolution television system. In one group a gelatin sponge soaked in 1.5 ml 16 mg/dl HA in water was applied topically at the time of injury and on postinjury days 1, 3, 5, and 7. The control group received the sponge soaked in the aqueous vehicle. Every 2 days after injury, the microcirculation was observed or histologic specimens were harvested. Wound size decreased almost twice as fast with HA compared with its vehicle (p less than 0.05). Healing was defined as time for total wound closure with at least one microvessel bridging the site of injury and required 16 or more days with vehicle but averaged less than 9 days with HA. Early during healing the repair site was surrounded by widespread extravasation of the fluorescent tracer, an index of inflammation; this area was reduced by two thirds 2 to 4 days after injury with HA compared with its vehicle (p less than 0.05). The density of perfused microvessels was twofold higher with HA 2 to 4 days after injury (p less than 0.05). However, microvessel density was similar in both groups by 6 days after injury and remained similar for at least 45 days after injury, which suggests that HA evoked no unusual angiogenic response. Histologic examination of fixed, stained specimens showed increases in intravascular leukocytes after injury and treatment-related differences in the distribution of intravascular leukocytes in 20 to 40 microns and 40 to 80 microns diameter microvessels 1 to 2 days after injury. Otherwise, leukocyte infiltration during healing was similar in both groups. The mechanism for the beneficial action of HA on healing is unknown. However, several in vitro studies suggest that HA is part of a feedback loop that promotes cell proliferation and migration in actively growing tissues. Alternatively, the role of HA in water homeostasis could favor tissue hydration, which has a well-known beneficial effect on healing.

Animals↗

PubMed1990

Actions of adenosine on nitro blue tetrazolium deposition and surface pH during intestinal reperfusion injury.

Mesenteric arteries supplying an intestinal segment were occluded for 5 minutes and then released. During reperfusion, two series of measurements were made with various substances topically applied to the extraluminal surface. In the first series, reduced nitro blue tetrazolium (NBT) was extracted from tissue and measured spectrophotometrically, as an index of oxidative damage. In the second series, mucosal and serosal surface pH was measured as an index of the functional ability to maintain ion gradients. In control conditions, NBT deposition averaged 55-63 micrograms/g tissue. After 60 and 120 minutes of reperfusion, NBT was elevated to 446-479 micrograms/g, which was approximately half as large as the NBT increment (846 micrograms/g) produced by a 15-minute application of xanthine plus xanthine oxidase to well-perfused tissue. As expected, NBT levels were significantly lower (299 micrograms/g) in tissue that was continuously suffused with superoxide dismutase (SOD) plus catalase (CAT) before occlusion and during reperfusion. Similar NBT levels (274 micrograms/g) were observed after reperfusion in animals that were fed a diet supplemented with the antioxidant vitamin E for 4-6 weeks. These observations affirm that some, but not all, NBT deposition after reperfusion can be attributed to oxyradicals. However, with exogenous adenosine (ADO) applied for the first 30 minutes after occlusion, NBT was elevated to 174 micrograms/g after 60 minutes, which was only half as large as the increment with SOD plus CAT, even though those substances were continuously applied. The opposite effect was produced by an ADO receptor antagonist, 8-phenyltheophylline; NBT was increased to 516 micrograms/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1990

Regional variations of laser Doppler blood flow in ischemic skin flaps.

An island skin flap was designed on the left inferior epigastric neurovascular bundle of anesthetized male rats. Blood flow was measured in situ with a laser Doppler flowmeter at 20 discrete points on a grid system (5 points in each quadrant of the flap) before and after surgery, or before vascular occlusion, during reperfusion, and 48 to 72 hours later. Two series of experiments were performed. In the first series, the raised flap was placed in a bath containing heated Ringer's solution and the left pedicle was cross-clamped. After 30 minutes, adenosine at a concentration that produced supramaximal vasodilatation, or its vehicle, was added to the bath. After 1 hour total occlusion time, the vascular clamp was released and adenosine treatment was continued for the first 30 minutes of reperfusion. In the second series, the protocol was similar except that adenosine, or its vehicle, was infused into the ischemic flap by means of the distal stump of the right inferior epigastric artery. After 48 to 72 hours, fluorescein was injected IV. The data showed a significant regional variation in baseline laser Doppler blood flow that was further altered by surgically raising the flap. Whereas proximal axial laser Doppler blood flow was essentially unchanged from the preoperative baseline, distal axial laser Doppler blood flow decreased 10 to 50 percent, and proximal and distal dependent laser Doppler blood flow decreased 50 to 80 percent. Thus no single value accurately reflected total flap perfusion. Necrosis occurred only in the dependent flap regions, which confirmed previous work. In the dependent regions, especially along the incision line, postoperative laser Doppler blood flow was lowest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1990

Temperature-sensitive adenosine-mediated vasoconstriction in the skin microcirculation.

The A1 and A2 adenosine receptor agonists (5'-(N-ethylcarboxamido)-adenosine, 2-chloroadenosine, adenosine (ADO) and N6-cyclohexyladenosine) were topically applied to 30- to 60-microns arterioles in the s.c. microcirculation of hamsters at different skin temperatures. Vasoconstrictor responses evoked by nanomolar concentrations of ADO and N6-cyclohexyladenosine were enhanced when local skin temperature (Ts) was increased, but unchanged when Ts was decreased. All these responses were antagonized by 8-phenyltheophylline, which suggests that temperature-sensitive vasoconstrictions were mediated by A1 receptors. In contrast, norepinephrine (10(-7) M) caused vasoconstrictions that were not enhanced at high Ts and were markedly reduced at low Ts, while angiotensin II (10(-8) M) caused vasoconstrictions that were temperature-insensitive. Vasodilator responses evoked by micromolar concentrations of ADO, 2-chloroadenosine and 5'-(N-ethylcarboxamido)-adenosine were temperature-insensitive. All these responses were antagonized by 8-phenyltheophylline, except those mediated by 10(-6) to 10(-4) M ADO, which can be explained by simple override of the receptor blockade. Thus, A1, but not A2, receptors show temperature-dependent actions in vivo, which suggests that temperature sensitivity could be an additional criterion for classification of ADO receptors.

Adenosine↗

PubMed1989

Pharmacological evidence for A1 and A2 adenosine receptors in the skin microcirculation.

To characterize adenosine-mediated vascular responses, synthetic A1 and A2 receptor agonists (N-ethyl carboxamido adenosine [NECA], 2-chloro adenosine [2CA], or cyclohexyl adenosine [CHA]), the parent compound (adenosine [ADO]), an uptake inhibitor (dipyridamole [DIPYRID]) or a nonselective, competitive antagonist (8-phenyl theophylline [8pTHEO]) were topically applied to 20-60 microns arterioles in the subcutaneous microcirculation of the hamster. Blood flow was calculated from arteriolar diameter and red blood cell velocity using intravital microscopy. At greater than 10(-8) M, the potency order for vasodilation (maximum, 170-190% of control) was NECA greater than 2CA greater than ADO; these responses were attenuated by 10(-5) M 8pTHEO. From 10(-8) to 10(-6) M, 2CA evoked vasodilation whereas ADO, which has an identical affinity at A1 and A2 receptors, evoked lesser responses. ADO-induced vasodilation was potentiated by 10(-5) M DIPYRID; this response was similar to that evoked by 2CA alone or 2CA + DIPYRID. In contrast to ADO, 2CA is a poor substrate for cellular uptake, which suggests that uptake reduces the A2 effect of exogenous ADO. From 10(-10) to 10(-8) M, CHA and ADO were equipotent antagonized by 8pTHEO. Norepinephrine was a more potent vasoconstrictor and 8pTHEO did not alter these responses. Since ADO is a metabolic substrate and a nonselective receptor agonist, while CHA is A1-selective and a poor substrate for cellular uptake, neither A2 activation nor cellular uptake altered expression of the A1 effect of exogenous ADO. Furthermore, DIPYRID had no effect on the A1 response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Attenuation of no-reflow phenomenon, neutrophil activation, and reperfusion injury in intestinal microcirculation by topical adenosine.

Small mesenteric arteries supplying partially isolated jejunal segments were totally occluded for 5 minutes and then released. With video microscopy, blood flow was calculated from measurements of submucosal arteriolar diameter and red blood cell velocity. For the first 30 minutes of reperfusion, the serosa was superfused with a Ringer's vehicle containing either adenosine (ADO; 10(-4) M), acetylcholine (ACh; 10(-5) M), or prostacyclin (PGI2; 3 x 10(-7) M). Thereafter, the substances were removed from the suffusate, and superfusion continued with vehicle alone for an additional 10-30 minutes. These concentrations were equieffective for causing vasodilation. During the first minute of reperfusion, blood flow increased more than 300% of baseline in all groups. Within the subsequent 30 minutes, blood flow fell to 45 +/- 3% of baseline with vehicle alone, which demonstrates the no-reflow phenomenon. While either ADO, ACh, or PGI2 was in the suffusate, vasodilation was persistent. After washout of these substances, the postocclusion blood flows were significantly higher with each treatment than with vehicle alone, which shows that each substance had a positive action. However, with ADO, blood flow was 121 +/- 7% of baseline after washout, whereas with ACh or PGI2, it was 64 +/- 10% or 69 +/- 5% of baseline after washout. This property of ADO was observed if the mucosa was superfused with a Ringer's solution or with a bile salt solution, which suggests that ADO might have similar properties in situ. After 60 minutes of reperfusion, the intestinal villi were short, thick, and edematous with epithelial necrosis and crypt degeneration. ADO attenuated most of these histological changes to a greater extent than either PGI2 or ACh. Furthermore, ADO reduced a biochemical index of neutrophil infiltration; tissue myeloperoxidase concentration was increased to 169 +/- 14% of baseline with vehicle but was increased to 120 +/- 8% with ADO. Overall, these observations suggest that ADO protects the intestine from ischemia-reperfusion injury by causing vasodilation and by inhibiting neutrophil function. The vasodilatory effect probably is a minor component because other vasodilators (ACh and PGI2) had minimal protective effects in these conditions.

Acetylcholine↗

PubMed1989

Cardiovascular and renal actions of cytochrome P-450 metabolites of arachidonic acid.

Cytochrome P-450 is the terminal oxidase of the electron transport chain the endoplasmic reticulum. Arachidonic acid (AA) can be oxidatively metabolized by cytochrome P-450 hemoproteins to an array of compounds identified as constituents of tissues and biological fluids. Their synthesis can be manipulated by pharmacologic probes and altered in pathophysiologic conditions. These novel eicosanoids stimulate release of peptide and steroid hormones, inhibit platelet and leukocyte aggregation, influence Na+-K+-atpase and alter vasomotor tone. They also participate in fluid and electrolyte homeostasis, stimulus-secretion coupling, and regulation of tissue blood flow. Since these novel AA metabolites may participate in receptor-mediated signal transduction, and have been implicated in the generation of second messengers and changes in intracellular calcium,these studies have important implications for understanding basic biological mechanisms.

Arachidonic Acid↗

PubMed1988

Arachidonic acid metabolites: basic concepts relevant to plastic surgery.

AA is the precursor of oxygenated metabolites called the eicosanoids, that are generated by the cyclooxygenase, lipoxygenase, or cytochrome P450 enzymatic pathways. The biologically active eicosanoids are labile, usually but not always, act near their site of synthesis, and are not stored in any tissue to any appreciable degree. In most tissues, there is a continuous low-level synthesis that is probably essential to normal function. Injury or surgical trauma can evoke a dramatic change in the quality and quantity of the metabolites. Pharmacologic manipulation of the pathways of AA metabolism, or alteration of the effects of AA metabolites, can significantly improve tissue perfusion in a variety of clinical situations. (See Figure 1 for a schematic summary of the pathways involved in arachidonic acid metabolites.

Animals↗

PubMed1988

Modulation of arteriolar blood flow by inhibitors of arachidonic acid oxidation after thermal injury: possible role for a novel class of vasodilator metabolites.

To examine the contribution of arachidonic acid (AA) metabolites to the maintenance of cutaneous vasomotor tone after thermal injury, enzyme inhibitors were topically applied to the hamster cheek pouch before and after a spot burn. By use of video microscopy, blood flow was measured in adjacent arterioles that supplied the injured site. Ringer's solutions containing no drug (vehicle), indomethacin (cyclooxygenase inhibitor), BW755c (cyclooxygenase/lipoxygenase inhibitor), or ketoconazole (lipoxygenase/cytochrome P450 inhibitor) continuously suffused the entire tissue. There were no effects of these drugs on preburn blood flow at concentrations that blocked the vascular effects evoked by topical AA. In all groups, blood flow transiently increased after burn and thereafter decreased to levels that were altered by treatment. These results could not be attributed to alterations in vascular reactivity because neither the burn nor the drugs altered the vasodilation evoked by adenosine or prostacyclin. Relative to Ringer's, indomethacin had no effect, BW755c caused vasodilation, and ketoconazole caused vasoconstriction, which suggests that cytochrome P450 products might be vasoactive mediators in injured tissue. Therefore, purified synthetic compounds were compared with known vasodilators. The potency was prostacyclin greater than 12R-hydroxyeicostetraenoic acid greater than adenosine = 5,6 epoxyeicosatrienoic acid greater than AA, which supports the hypothesis that AA can be the source of a novel class of nonprostaglandin vasodilator compounds. In addition, at least one of the vasodilator responses was stereospecific. Nevertheless, the exact explanation for the differential effects of AA inhibitors on postburn blood flow is unknown.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1987

Intestinal vasodilation by epoxyeicosatrienoic acids: arachidonic acid metabolites produced by a cytochrome P450 monooxygenase.

Purified synthetic products from the cytochrome P450 pathway of arachidonate metabolism were applied to the intestinal serosa. Arteriolar blood flow was calculated using video microscopy. After a steady-state baseline, a bolus containing 10-60 micrograms 14,15-epoxyeicosatrienoic acid/ml (14,15-EET) had no detectable effect on blood flow. However, 25 +/- 3 micrograms 11,12-EET/ml and 36 +/- 2 micrograms 8,9-EET/ml caused increases (134 +/- 8% and 127 +/- 6%) that were similar to those elicited by 8 +/- 2 micrograms adenosine/ml (138 +/- 12%). Furthermore, the increases (275 +/- 38%) produced by 32 +/- 6 micrograms 5,6-EET/ml exceeded those elicited (160 +/- 10%) by a similar concentration (27 +/- 3 micrograms/ml) of adenosine. Thus, a structure-activity relationship is suggested. Nevertheless, these values probably underestimate the potency of the EETs because the vasoactivity was reduced by contact with water. The activity of the cyclooxygenase pathway seemed to limit the formation of vasoactive quantities of EETs, or other nonprostanoids, from exogenous arachidonate in the serosa but not the mucosa. A bolus (1.3 +/- 0.2 mg/ml) or continuous application (122 +/- 45 micrograms/ml) of arachidonate caused blood flow increases (236 +/- 14% or 229 +/- 27%) that were almost eliminated (129 +/- 5% or 121 +/- 9%) by a cyclooxygenase inhibitor; the residual response was abolished by a cytochrome P450 inhibitor. However, cytochrome P450 inhibitors alone did not attenuate the arachidonate response. In contrast, a continuous application of 194 micrograms arachidonate/ml to the mucosa caused a markedly smaller blood flow increase (119 +/- 8%) and cyclooxygenase inhibitors potentiated (132 +/- 8%), rather than reduced, this response. We conclude that EETs are a labile class of vasodilators with a potency comparable to adenosine in the intestinal microcirculation. Indirect evidence suggests regional differences in the formation of vasoactive quantities of arachidonate metabolites within the intestinal wall.

8,11,14-Eicosatrienoic Acid↗

PubMed1987

Selective antagonism of hormone-induced vasoconstriction by synthetic atrial natriuretic factor in the rat microcirculation.

Synthetic atrial natriuretic factor (ANF) was either added to suffusate solutions (30 nM) or infused into the jugular vein (0.1 nanomol/min/100 g) of anesthetized rats. Steady-state blood flow was calculated from arteriolar diameter and red blood cell velocity measurements using video microscopy in the intestinal or skeletal muscle microcirculation. Arterioles demonstrated spontaneous vasomotor tone by dilating to topical adenosine, but topical or intravenous ANF did not cause vasodilation. Either angiotensin, norepinephrine, or vasopressin was added to the suffusates in the presence or absence of a cyclooxygenase inhibitor (30 microM, meclofenamate or indomethacin) because each agonist is known to stimulate vasoactive prostanoid synthesis. In the intestine, angiotensin (500 nM) caused 40 +/- 2% blood flow decreases during intravenous saline but only 23 +/- 6% during intravenous ANF. Angiotensin (162 nM) and a cyclooxygenase inhibitor caused 19 +/- 4% blood flow decreases but only 8 +/- 5% decreases with cyclooxygenase inhibitor and topical ANF. In contrast, norepinephrine (2-5 microM) caused vasoconstriction that was not altered by topical or intravenous ANF, either alone or in combination with cyclooxygenase inhibitors. In the spinotrapezius muscle, angiotensin (1-2 nM) plus a cyclooxygenase inhibitor caused 40-60% blood flow decreases but only 20-30% decreases during intravenous or topical ANF. Topical or intravenous ANF did not alter the vasoconstriction evoked by arginine vasopressin (0.5-1.0 nM) or by norepinephrine (40-230 nM). Thus, supraphysiologic concentrations of ANF produced no direct vasodilation in the intestinal or skeletal muscle microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed1987

Intestinal arteriolar responses to mucosal and serosal applications of adenosine analogues.

Adenosine or its synthetic analogues were topically applied to the intestinal jejunum while steady-state blood flow was calculated in submucosal arterioles using video microscopy. Blood flow increased (220 or 130% of control) with the serosal application of 10(-6) M N-ethyl carboxamido adenosine (NECA, A2-selective agonist) or 2-chloro adenosine (2CA, nonselective agonist) but not with cyclohexyl adenosine (CHA, A1-selective agonist). The nonselective competitive antagonist, 8-phenyl theophylline, attenuated the response evoked by NECA. The mucosal application of 10(-6) M CHA caused blood flow decreases (81% of control), but neither NECA nor 2CA evoked a response. These observations suggest a mucosal diffusion barrier, so the concentrations of the analogues were raised one hundredfold. Serosal 10(-4) M CHA or NECA caused blood flow increases, but the effects were negligible with mucosal application, suggesting that the mucosa was indeed impermeable to these compounds. The responses evoked by 10(-4) M 2CA were similar on the serosa or mucosa (200-220% of control), submaximal (maximum = 400% of control at 10(-3) M), and not antagonized by 8-phenyl theophylline or by the cellular uptake inhibitor, nitrobenzyl-6-thio guanosine. In context with earlier studies, greater than 10(-6) M 2CA probably evokes vasodilation that is not entirely mediated by extracellular receptors. Serosal adenosine (10(-4) M) caused submaximal blood flow increases (200% of control) that were not potentiated by nitrobenzyl-6-thio guanosine or another transport inhibitor, dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Chloroadenosine↗

PubMed1987

Preoptic hypothalamic control of arteriolar vasodilatory responses.

Arteriolar responses to hemorrhage were directly observed in the skeletal muscle and intestinal circulations of two groups of animals. In one group, the periventricular tissue surrounding the anteroventral portion of the third cerebral ventricle (AV3V) was electrolytically lesioned 7-10 days before an acute experiment. In the other group, control surgical procedures were performed. Hemorrhage resulted in similar decreases in arterial blood pressure (30-60% prehemorrhage level) and intestinal blood flow (20-60% prehemorrhage level) in both groups. In contrast, arteriolar diameter significantly increased following hemorrhage in the spinotrapezius muscle of control-operated animals (141 +/- 9% prehemorrhage level) but did not change in animals with AV3V lesions (97 +/- 7% prehemorrhage level). In a previous study, electrical stimulation of intact AV3V tissue was shown to cause a sustained decrease in blood pressure (80-90% of control level) and a vasodilation in skeletal muscle arterioles (120-140% control level). Since stimulation of intact AV3V tissue evokes vasodilation and AV3V tissue ablation reduces hemorrhage-induced vasodilation, this region of the hypothalamus may play an important role in the regulation or modulation of some responses in the peripheral microcirculation.

Animals↗

PubMed1986

Skeletal muscle vasodilation during electrical stimulation of the preoptic recess.

Transverse (3rd-order) arterioles (diam 12 +/- 2 micron, n = 6) in rat spinotrapezius muscle were observed with video microscopy during electrical stimulation of preoptic recess in periventricular region of hypothalamus (AV3V region) to test whether active skeletal muscle vasodilation was mediated by a beta-adrenergic mechanism. Bipolar wire electrodes were implanted in AV3V 3-7 days before an experiment. Continuous superfusion of propranolol (10(-5) M) caused steady-state reduction (3 +/- 1 microns) in arteriolar diameter and reduced steady-state vasodilation (26 +/- 2 vs. 11 +/- 2 microns) caused by a continuous superfusion of isoproterenol (10(-6) M). Six arterioles were observed with and without propranolol during four frequencies of AV3V stimulation (8-15 V, 0.2-0.5 ms pulse duration; 10, 15, 20, and 25 Hz; 1 min stimulus duration). Stimulation caused frequency-related reductions in arterial blood pressure (10-20 mmHg), which were sustained and not altered by propranolol. Transient peak diameters were observed after 30 +/- 7 s; the time was not related to stimulus frequency or affected by propranolol. Peak diameters averaged 14-17 microns during vehicle and 11-12 micron during propranolol (maximum diam 32 +/- 3). Peak vasodilations were significant but identical with vehicle or propranolol (avg 3 +/- 1 microns) and not related to stimulus frequency. Diameters stabilized at steady-state values above base line only during 15 and 20 Hz with vehicle and only during 20 Hz with propranolol. We conclude that AV3V stimulation causes transient vasodilation in spinotrapezius muscle that is probably not mediated by beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Possible role for adenosine in local regulation of absorptive hyperemia in rat intestine.

To test whether extracellular adenosine participates in the local regulation of intestinal blood flow during nutrient absorption, the serosa of the jejunum was continuously suffused with adenosine deaminase (7 micrograms protein/ml) or theophylline (10(-4) M) in Ringer's solution. Using video microscopy, blood flow was calculated in submucosal arterioles from diameter and red cell velocity measurements. After a steady-state baseline, oleic acid (20 mM) + glucose (56 mM) were added to a bile salt solution suffusing the mucosa. Baseline arteriolar diameters and blood flows were 52 +/- 2 micron and 20 +/- 2 nl/sec with the serosal suffusate containing Ringer's; these values were not significantly altered by theophylline or deaminase treatment. During suffusion of the mucosa with a nutrient solution, diameter and blood flow transiently increased and these responses were not altered by deaminase or theophylline. Thereafter, diameter and blood flow stabilized at lower values for the duration of absorption. Diameter and blood flow were increased to 111 +/- 1% and 134 +/- 5% of control during absorption with Ringer's; the corresponding values were significantly lower with deaminase or theophylline. After absorption, diameter and blood flow stabilized near baseline with Ringer's within 7-12 minutes; the corresponding values were significantly lower with deaminase or theophylline for at least 30 minutes. Since deaminase and theophylline produced similar effects on absorptive hyperemia, adenosine might participate with other factors in the local regulation of that response. Adenosine applied to the serosa caused dose-dependent increases in calculated blood flow with a threshold near 10(-5) M and a maximum near 10(-3) M. In contrast, even 10(-2) M adenosine in the mucosal suffusate did not increase blood flow above baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗