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Dilatation and constriction of rat gastric mucosal microvessels through prostaglandin EP2 and EP3 receptors.

BACKGROUND: Prostaglandin (PG)E2 has both a vasodilating action and a protective function in the gastric mucosa. There are four subtypes of PGE2-sensitive, or EP, receptors. AIM: To identify the subtype of EP receptors in the microvessels of the rat gastric mucosa using EP2 and EP3 receptor agonists. METHODS: The posterior wall of the anaesthetized rat stomach was secured in a chamber and superfused with Tyrode's solution, and the gastric microcirculation of the mucosal base was observed through a window with transillumination. PGE2 and its derivatives (20 microL) were applied topically in the window. RESULTS: PGE2 (0.001-10 micromol/L), misoprostol (EP2/EP3 receptor agonist; 0.01-100 micromol/L) and butaprost (EP2 receptor agonist; 1-1000 micromol/L) dilated the arterioles dose-dependently, but M&B 28 767 (EP3 receptor agonist; 0.001-10 micromol/L) did not alter their diameters. M&B 28 767 constricted the venules and collecting venules dose-dependently whereas butaprost dilated them. PGE2 and misoprostol had bell-shaped dose-response curves: constriction by low doses of PGE2 and misoprostol (0.001-0.1 micromol/L and 0.01-1 micromol/L) and dilation by high doses of PGE2 and misoprostol (0.1-100 micromol/L and 1-100 micromol/L). CONCLUSIONS: These results suggest that PGE2 dilated both arterioles and venules in the rat gastric mucosa through the EP2 receptors and constricted the venules through the EP3 receptors.

Alprostadil↗

Prenatal constriction of the fetal ductus arteriosus--related to maternal pain medication?

Physiological fetal circulation requires patency of the ductus arteriosus. As gestation proceeds, the sensitivity of the ductus to dilating prostaglandins diminishes. The sensitivity to constricting agents like PGE-synthetase inhibitors, present in many analgetics, however, increases. Fetuses affected by an antenatal constriction of the ductus arteriosus (DC) may present with different signs of cardiac failure including dilated right ventricle, tricuspid regurgitation and abnormal venous Doppler. We report on four cases with prenatal DC, presenting at 34, 35, 36 and 37 weeks of gestation. They were referred to fetal echocardiography because of abnormal routine echo scans with unexplained signs of right heart decompensation. Three patients were medicated during pregnancy with either aspirin (low dose), metamizole or ibuprofen. One patient did not take any drugs, especially no pain medication drug in pregnancy. Immediate delivery was performed in all cases. The neonates were in a good condition; echocardiography showed different degrees of right heart hypertrophy which disappeared in all infants by the age of 3 months except in case 2. Unexplained fetal right heart decompensation requires detailed echocardiographic evaluation of the ductus arteriosus and a sophisticated medical history with regard to analgesics. In contrast to ibuprofen and high-dose aspirin, metamizole and low-dose aspirin have not yet been reported as possible agents constricting the fetal arterial duct. In any suspected context, early delivery as in our cases may save babies life. Any application of non-steroidal anti-inflammatory drugs in pregnancy requires close fetal follow-up due to their potentially life-threatening effect.

Analgesics, Non-Narcotic↗

Inactivation of FtsI inhibits constriction of the FtsZ cytokinetic ring and delays the assembly of FtsZ rings at potential division sites.

A universally conserved event in cell division is the formation of a cytokinetic ring at the future site of division. In the bacterium Escherichia coli, this ring is formed by the essential cell division protein FtsZ. We have used immunofluorescence microscopy to show that FtsZ assembles early in the division cycle, suggesting that constriction of the FtsZ ring is regulated and supporting the view that FtsZ serves as a bacterial cytoskeleton. Assembly of FtsZ rings was heterogeneously affected in an ftsI temperature-sensitive mutant grown at the nonpermissive temperature, some filaments displaying a striking defect in FtsZ assembly and others displaying little or no defect. By using low concentrations of the beta-lactams cephalexin and piperacillin to specifically inhibit FtsI (PBP3), an enzyme that synthesizes peptidoglycan at the division septum, we show that FtsZ ring constriction requires the transpeptidase activity of FtsI. Unconstricted FtsZ rings are stably trapped at the midpoint of the cell for several generations after inactivation of FtsI, whereas partially constricted FtsZ rings are less effectively trapped. In addition, FtsZ rings are able to assemble in newborn cells in the presence of cephalexin, suggesting that newborn cells contain a site at which FtsZ can assemble (the nascent division site) and that the transpeptidase activity of FtsI is not required for assembly of FtsZ at these sites. However, aside from this first round of FtsZ ring assembly, very few additional FtsZ rings assemble in the presence of cephalexin, even after several generations of growth. One interpretation of these results is that the transpeptidase activity of FtsI is required, directly or indirectly, for the assembly of nascent division sites and thereby for future assembly of FtsZ rings.

Bacterial Proteins↗

Crystal structure of AqpZ tetramer reveals two distinct Arg-189 conformations associated with water permeation through the narrowest constriction of the water-conducting channel.

AqpZ is a homotetramer of four water-conducting channels that facilitate rapid water movements across the plasma membrane of Escherichia coli. Here we report a 3.2 angstroms crystal structure of the tetrameric AqpZ (tAqpZ). All channel-lining residues in the four monomeric channels are found orientated in nearly identical positions with one marked exception at the narrowest channel constriction, where the side chain of a highly conserved Arg-189 adopts two distinct conformational orientations. In one of the four monomers, the guanidino group of Arg-189 points toward the periplasmic vestibule, opening up the constriction to accommodate the binding of a water molecule through a tridentate H-bond. In the other three monomers, the Arg-189 guanidino group bends over to form an H-bond with carbonyl oxygen of the Thr-183, thus occluding the channel. Therefore, the tAqpZ structure reveals two distinct Arg-189 confirmations associated with water permeation through the channel constrictions. Alternation between the two Arg-189 conformations disrupts continuous flow of water, thus regulating the open probability of the water pore. Further, the difference in Arg-189 displacements is correlated with a strong electron density found between the first transmembrane helices of two open channels, suggesting that the observed Arg-189 conformations are stabilized by asymmetrical subunit interactions in tAqpZ.

Aquaporins↗

Nonparticulate components of diesel exhaust promote constriction in coronary arteries from ApoE-/- mice.

Air pollution is positively associated with increased daily incidence of myocardial infarction and cardiovascular mortality. We hypothesize that air pollutants, primarily vapor phase organic compounds, cause an enhancement of coronary vascular constriction. Such events may predispose susceptible individuals to anginal symptoms and/or exacerbation of infarction. To develop this hypothesis, we studied the effects of nonparticulate diesel exhaust constituents on (1) electrocardiographic traces from ApoE-/- mice exposed whole-body and (2) isolated, pressurized septal coronary arteries from ApoE-/- mice. ApoE-/- mice were implanted with radiotelemetry devices to assess electrocardiogram (ECG) waveforms continuously throughout exposures (6 h/day x 3 days) to diesel exhaust (0.5 and 3.6 mg/m3) in whole-body inhalation chambers with or without particulates filtered. Significant bradycardia and T-wave depression were observed, regardless of the presence of particulates. Pulmonary inflammation was present only in the whole exhaust-exposed animals at the highest concentration. Fresh diesel exhaust or air was bubbled through the physiologic saline tissue bath prior to experiments to enable the isolated tissue exposure; exposed saline contained elevated levels of several volatile carbonyls and alkanes, but low to absent levels of polycyclic aromatic hydrocarbons. Vessels were then assayed for constrictive and dilatory function. Diesel components enhanced the vasoconstrictive effects of endothelin-1 and reduced the dilatory response to sodium nitroprusside. These data demonstrate that nonparticulate compounds in whole diesel exhaust elicit ECG changes consistent with myocardial ischemia. Furthermore, the volatile organic compounds in the vapor phase caused enhanced constriction and reduced dilatation in isolated coronary arteries caused by nonparticulate components of diesel exhaust.

Air Pollutants↗

Effect of sevoflurane and desflurane on the myogenic constriction and flow-induced dilation in rat coronary arterioles.

BACKGROUND: Determinants of myocardial blood flow distribution include metabolic, myogenic, endothelial, and neurohumoral control mechanisms. The authors studied the effect of sevoflurane and desflurane on the myogenic and endothelial mechanisms. METHODS: Wistar rat subepicardial microvessels, approximately 100 microm in diameter, were monitored for diameter changes in vitro using a video detection system. Myogenic vasomotion was studied by varying the intraluminal pressure from 10 mmHg to 120 mmHg. Flow-induced, endothelium-dependent dilation was evaluated in U46619-preconstricted vessels by varying the pressure gradient across the isolated vessel from 10 mmHg to 80 mmHg, while maintaining the midpoint luminal pressure constant at 40 mmHg to avoid myogenic effects. Myogenic and flow-induced vasomotion both were studied in the presence of sevoflurane, 1 or 2 minimum alveolar concentration (MAC) (MAC is a unit of inhalational anesthetic potency), desflurane, 1 or 2 MAC, or no anesthetic (control). RESULTS: Myogenic constriction was shown above intraluminal pressures of 70 mmHg. Myogenic constriction was unchanged by sevoflurane, 1 MAC (P = 0.24), but was mildly enhanced by sevoflurane, 2 MAC (P < 0.05), or desflurane, 1 (P < 0.05) or 2 MAC (P < 0.01). Flow-induced dilation was shown over the pressure gradient range of 10-80 mmHg. Flow-induced dilation was not altered significantly by sevoflurane, 1 or 2 MAC (P > 0.3 each), but was significantly attenuated by desflurane, 1 or 2 MAC (P < 0.001 each). CONCLUSIONS: Sevoflurane maintains myogenic and endothelial determinants of myocardial blood flow distribution. Conversely, desflurane attenuates endothelium-dependent flow-induced dilation while mildly enhancing myogenic constriction.

Anesthetics, Inhalation↗

Immunoneutralization of c-Fos using intrathecal antibody electroporation attenuates chronic constrictive injury-induced hyperalgesia and regulates preprodynorphin expression in rats.

BACKGROUND: In vivo electroporation has been successfully used for the introduction of DNA, RNA, oligonucleotides, and proteins into cells for experimental and therapeutic purposes. The authors evaluated the efficacy of electroporation-mediated c-Fos antibody therapy for neuropathic pain in vitro and in vivo. METHODS: First, the authors studied the inhibitory effects of intrathecal c-Fos antibody electroporation on the activating protein (AP-1) promoter activity in cultured spinal neuronal cells transfected with p-AP-Luc plasmid and activated with 100 microm glutamate. The inhibitory effect of c-Fos antibody electroporation in the regulation of AP-1 promoter activity was assessed according to the relative luciferase activity. Second, rats with chronic constrictive injury underwent electroporation treatment for neuropathic pain using c-Fos antibody. Thermal nociceptive thresholds were measured before chronic constrictive injury and then on even-numbered days, up to and including day 14, to assess and compare the therapeutic effects of intrathecal electroporation. The time course was assessed by Western blot analysis and by immunohistochemical analysis. Pronociceptive gene expression was measured by assessing prodynorphin mRNA and dynorphin peptides on days 2 and 10 after intrathecal c-Fos electroporation. RESULTS: Cotransfection of c-Fos antibody significantly decreased glutamate-induced AP-1 activity. Intrathecal electrotransfer of c-Fos antibody attenuated spinal dynorphin levels, as manifested by significantly elevated pain thresholds in the chronic constrictive injury-affected limbs. CONCLUSION: This study shows that transfer of antibody into rat spinal cords by intrathecal electroporation is a useful method to study the function of endogenous factors of spinal-related disorders.

Animals↗

Correction of constricted ear.

We present a case of moderate constricted ear corrected using a modified Tanzer's technique for the helical deformity and lengthening the lower third of the pinna with a cutaneous transposition flap from the retroauricular area. The operation begins with a rapid intraoperative expansion of the retroauricular skin. Then an incision is made on the posteromedial ear aspect and the ear is degloved using a subperichondral plane. The upper pole of the cartilage is expanded and rearranged by an anteriorly pedicled helical flap and a cartilaginous graft is taken from the constricted part of the concha. The lower third of the pinna is lengthened by a cutaneous transposition flap from the retroauricular area. Thus, the ear is lengthened and the skin that otherwise tends to maintain its "constricted" form relapses. A second surgical stage is performed, under local anesthesia, to cut the pedicle of the retroauricular transposition flap. This method consents an adequate correction of the shape and an effective expansion, of about 1 cm, in the length of the pinna.

Adult↗

Classification of the pattern of intrauterine amputations of the upper limb in constriction ring syndrome.

Twenty patients with congenital upper limb amputations caused by constriction rings were reviewed to classify the pattern of these amputations. In the 20 patients studied, 31 upper limbs had congenital amputations. The pattern of amputation was classified into three types. Proximal upper limb amputation was considered type I and was only seen in one limb. The most common pattern of amputation was digital amputation associated with "coning" or "superimposition" of the digits (type II) and was seen in 20 hands. Type II amputations were subclassified according to the involvement of all, ulnar, radial, or central digits by the constriction ring. In type III amputations (N = 10 limbs), there was no associated coning or superimposition of the digits. This type of amputation was subclassified into type IIIA (multiple-digit amputations within the same hand) and type III B (single-digit amputation). Associated anomalies are reviewed and the pathogenesis of constriction rings is discussed.

Amniotic Band Syndrome↗

Effect of pharmacological dilation and constriction of pupil on corneal topography.

A prospective study was undertaken to investigate the effect of pharmacological pupillary dilation and constriction on corneal topography. Corneal topography was performed using the EyeSys system on 28 normal subjects before and after pupil dilation, constriction, and then with the pupil intact (no medication). Our results show that both flattening and steepening of the corneal curvature were found in all three examination periods. The numbers of corneas with flattening and steepening in each examination period were compared and found not to be statistically different. Mean change of corneal flattening was compared with mean change of corneal steepening in each examination period and again no significant difference was found. These results indicate that the slight changes in corneal power and radius following pharmacological pupillary dilation or constriction may be due to either the inability to repeat by the subjects, or error by observers or instrument.

Adult↗

The effect of pulmonic and aortic constriction on regional left ventricular thickening dynamics, geometry and the radius of septal curvature. Analysis by gated computed transmission tomography.

We evaluated the effects of aortic and pulmonic constriction on cross-sectional cardiac dynamics using prospectively gated computed transmission tomography (CT) in six dogs in order to evaluate 1) the effect of altering the end-diastolic trans-septal pressure gradient on the radius of septal curvature, and 2) the effect of right ventricular overload on regional left ventricular geometry and wall thickening dynamics. Cross-sectional CT data were obtained in a control state, at two incrementally higher levels of right ventricular end-diastolic pressure produced by constriction of the pulmonary artery (PA1 and PA2) and then at one higher level of left ventricular end-diastolic pressure resulting from acute aortic constriction (Ao). Using fluid-filled polyethylene catheters, we measured right and left ventricular pressures simultaneous with the image acquisition. The measured radius of septal curvature was then normalized by the calculated average radius derived from the left ventricular area at end-diastole. The end-diastolic radius of septal curvature ratio increased as delta [LVEDP-RVEDP] declined (from 1.03 +/- 0.13 at control; 1.20 +/- 0.18 PA2; 1.27 +/- 0.14 PA2 and 0.87 +/- 0.11 Ao). As this LVEDP-RVEDP gradient declined (ie, RVEDP increased in proportion to LVEDP) septal wall thickening declined (P less than 0.005), with significantly less change in left ventricular anterior or lateral wall thickening. With PA hypertension, LV end-diastolic volume and percent delta volume significantly declined (P less than 0.005) while RV end-diastolic volume increased. With PA pressure overload, septum-free wall distance declined (P less than 0.01) as did percent shortening along this dimension (P less than 0.01). We conclude that predictable changes in LV and RV dynamics occur when trans-septal pressure gradients change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparative effects of diltiazem, nifedipine, and verapamil on large and small coronary artery constriction induced by intracoronary acetylcholine in pigs.

The in vivo protective effects of diltiazem, nifedipine, and verapamil on large and small coronary artery constriction induced by intracoronary injection of acetylcholine were compared by coronary arteriography in pigs. The percent narrowing of the epicardial major right coronary artery was used as an indicator of large coronary artery constriction, and the time required for contrast medium to reach the posterior descending coronary artery from the ostium of the right coronary artery was used as an indicator of small coronary artery constriction. Doses of 12.5, 25, 50, 100, and 200 micrograms of acetylcholine were administered into the right coronary artery under left ventricular pacing to keep the systemic hemodynamics constant. Marked prolongation of the flow time of contrast medium to greater than or equal to 8.1 s (control of less than or equal to 1.8 s) with mild narrowing of the epicardial major right coronary artery (less than or equal to 35%) was observed at doses of 12.5-50 micrograms of acetylcholine and was accompanied by myocardial ischemia. Over 50% narrowing of the epicardial major coronary artery plus markedly slow flow of contrast medium were induced in 12 of the 15 pigs by 100-200 micrograms of acetylcholine. Narrowing of the epicardial major coronary artery and the delay time of contrast medium flow induced by acetylcholine were both significantly reduced to 12-33% (control: 36-81%) and to 4.3-16.8 s (control: 16.2-37.7 s) after intracoronary injection of 100 micrograms of diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Possible mechanisms for the venular constriction elicited by Ruscus extract on hamster cheek pouch.

We investigated the influence of alpha-adrenoceptors blockers and calcium blockers on the effects of the venotonic agent Ruscus extract on the diameter of arterioles (ID 10-70 microns) and venules (ID 20-135 microns) of hamster cheek pouch microvasculature in vivo. For microcirculatory measurements, the preparations were placed under an intravital microscope coupled to a closed-circuit TV system. The TV monitor display was used to obtain arteriolar and venular internal diameter recordings (always at the same site) by an image shearing device. All drugs were applied topically. Ruscus extract was tested in different concentrations and in combination with prazosin (alpha 1-adrenoceptor antagonist), rauwolscine (alpha 2-adrenoceptor antagonist), or diltiazem (calcium blocker). Topical application of Ruscus extract elicited concentration-dependent responses in the studied vessels: arterioles remained unchanged in the concentration range tested, whereas venules remained unchanged or constricted depending on the concentration used. The observed venular constriction could be blocked by low concentrations (10(-9) M) of prazosin or diltiazem and by high concentrations (> 10(-6) M) of rauwolscine. Our results suggest that the venular constriction elicited by Ruscus extract in vivo, at the microcirculatory level, is mediated by calcium and by alpha-adrenoceptors and further support data previously reported on larger vessels and on patients with venous insufficiency.

Adrenergic alpha-Antagonists↗

Radial, ulnar, and median nerve palsies caused by a congenital constriction band of the arm: single-stage correction.

Single-stage correction of a congenital constriction band of the arm in an infant with radial, ulnar, and median nerve dysfunction is reported with significant improvement in neurologic function. This was accomplished by thorough preoperative physical examination and neurologic evaluation, circumferential excision of the constricting band, decompression of the involved peripheral nerves, and multiple large Z-plasties for skin closure. Based on the case presented here and a review of the literature, management of patients with congenital constriction rings overlying major nerve trunks should include (1) complete neurologic examination, even in the infant, (2) electromyographic and nerve conduction studies if there is any evidence of nerve dysfunction, (3) early complete excision of the band in one stage if there is no evidence of edema seen with lymphatic or venous obstruction (otherwise, two-stage removal of the band should be planned), and (4) early exploration and decompression of all major peripheral nerves beneath the band if there is any neurologic dysfunction.

Amniotic Band Syndrome↗

5-year series of constricted (lop and cup) ear corrections: development of the mastoid hitch as an adjunctive technique.

Despite the multitude of corrective procedures described, adequate surgical correction of the congenital constricted ear remains a challenge. The maintenance of the shape and elevation of the reconstructed upper neohelix poses a particular problem. In the present series, experiences with lop ear correction utilizing standard techniques and the use of the mastoid hitch as a useful adjunct to these procedures are described. A total of 19 ears were reconstructed. There were three type 1, eight type 2a, seven type 2b, and one type 3 deformities (Tanzer classification). A graded sequence of procedures was adopted. Mild deformities were corrected by cartilage scoring techniques; a V-Y advancement of the helical root was added for moderate deformities. Cartilage expansion by a banner flap was required for more severe deformities. A mastoid hitch, whereby the refashioned upper neohelix is sutured to the mastoid fascia, should be used as an adjunct to these procedures to maintain helical elevation and prevent recurrence. Severe type 3 deformities may require autologous auricular reconstruction. Mean follow-up time was 1 year. There were six excellent, seven good, four fair, and two poor results. Two patients who had not had mastoid hitch procedures developed a recurrence of the lop deformity. Adequate surgical correction of constricted ear deformities requires a variety of surgical techniques. The mastoid hitch being used for constricted ear correction has not been described elsewhere. The mastoid hitch is a useful adjunctive procedure that may be used effectively in combination with other procedures.

Adolescent↗

Altered myogenic constriction and endothelium-derived hyperpolarizing factor-mediated relaxation in small mesenteric arteries of hypertensive subtotally nephrectomized rats.

OBJECTIVES: Chronic renal failure (CRF) is associated with altered systemic arterial tone and hypertension. Myogenic constriction and endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation represent major vasoregulatory mechanisms in small systemic arteries. Elevated myogenic response and impaired EDHF might participate in the development of essential hypertension; however, their role in CRF-related hypertension is unknown. We investigated whether myogenic response and EDHF are altered in subtotally nephrectomized (sNX) rats and whether these changes are modifiable by chronic treatment with angiotensin-converting enzyme (ACE) inhibitor. METHODS: In a pressure arteriograph, myogenic constriction and EDHF-mediated relaxation were evaluated in small mesenteric arteries isolated from male Wistar rats 15 weeks after either sham operation (n = 7) (SHAM), sNX (n = 12) or sNX followed by 9 weeks of treatment with lisinopril (sNX + LIS, 2.5 mg/kg, n = 13). RESULTS: Surprisingly, myogenic response was reduced in hypertensive CRF rats (maximal myogenic tone: 37 +/- 2 and 18 +/- 4%, P < 0.01; peak myogenic index: -0.80 +/- 0.08 and -0.40 +/- 0.12%/mmHg, P < 0.05 in SHAM and sNX respectively). At the same time EDHF-mediated relaxation was also impaired (maximal response: 92 +/- 2 and 77 +/- 5%, P < 0.01; pD2: 6.5 +/- 0.1 and 5.9 +/- 0.1, P < 0.05). Both myogenic response and EDHF were inversely related to the severity of renal failure and restored by treatment with lisinopril to levels found in SHAM animals. CONCLUSION: Major constrictive (myogenic) and dilatory (EDHF) mechanisms of small systemic arteries are impaired in hypertensive CRF rats. These alterations do not seem to participate in the development of hypertension, being rather directly related to the severity of renal impairment. Both systemic vascular changes might be restored by renoprotective treatment with ACE inhibitor.

Angiography↗

Congenital constriction band syndrome.

Eighty-three patients with congenital constriction band syndrome were reviewed. Clinical manifestations and associated anomalies were analyzed with attention directed to distribution of the involvement. Constriction bands, amputation, and acrosyndactyly were the main clinical manifestations of this syndrome. Involvement of the distal portions of the extremity was most common. In the hand, the central digits were involved most frequently, and the thumb was only minimally affected in most cases. Of the 19 cases with an associated clubfoot deformity, 10 were proven to be a paralytic clubfoot due to compression neuropathy of the peroneal nerve caused by a deep constriction band below the knee, whereas 9 had a normal peripheral nerve.

Amniotic Band Syndrome↗

Congenital constriction band syndrome.

A retrospective study of 55 patients with congenital constriction band syndrome was performed. Multiple extremity involvement was found to be the most common clinical feature associated with the disease, and 34% of the patients studied were premature at birth. Malformations included constriction bands, clubfoot, intrauterine amputation, syndactyly, and acrosyndactyly (fenestrated syndactyly). The extremities were most often affected distally, involving the longer central fingers and medial two toes. More proximal involvement with constriction bands was associated with a higher frequency of neurologic deficit. Significant leg-length discrepancy exceeding 2.5 cm was seen in 9 of 38 patients (24%) with lower extremity involvement, a condition that has not been previously reported.

Abnormalities, Multiple↗