Mechanism Of Constriction Research Articles

Reversal of hypercapnia induces K ATP channel and NO-independent constriction of basilar artery in rabbits with acute metabolic alkalosis

The mechanism of hypocapnic constriction of the cerebral vasculature under conditions of altered acid–base balance has not been investigated. As K ATP channels and NO have been implicated in hypocapnic constriction, this study investigated their roles in the constriction due to lowered pCO 2 in hypercapnic rabbits with acute metabolic alkalosis. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. Lowering blood pCO 2 from initial baseline hypercapnic levels to near normocapnic and hypocapnic levels constricted basilar artery by 10.2±0.8% (4) and 16.2±0.6% (44), respectively (means±S.E., n), as determined in an in situ cranial window preparation. The constrictions were maintained for 4–5 h and return of pCO 2 to hypercapnic levels relaxed the constriction. Changing the suffusate pH to either the pH of the cerebral spinal fluid observed during initial baseline hypercapnia or following lowered pCO 2 did not alter the magnitude of constriction due to lowered pCO 2. Neither 0.3 mM N G-monomethyl- l-arginine monoacetate, an NO synthase inhibitor, nor 10 μM glibenclamide, a K ATP channel blocker, altered the magnitude of hypocapnic constriction. These results demonstrated that under conditions of acute metabolic alkalosis and accompanying compensatory hypercapnia, subsequent pCO 2 reduction induces prolonged constriction of the basilar artery that is independent of (1) cerebral spinal fluid pH over a physiologic range, and (2) NO and K ATP channels.

Increased Ca2+ sensitivity as a key mechanism of PKC-induced constriction in pressurized cerebral arteries.

The effects of activating protein kinase C (PKC) with indolactam V (Indo-V) and 1,2-dioctanoyl-sn-glycerol (DOG) on smooth muscle intracellular Ca2+ concentrations ([Ca2+]i) and arterial diameter were determined using ratiometric Ca2+ imaging and video edge detection of pressurized rat posterior cerebral arteries. Elevation of intraluminal pressure from 10 to 60 mmHg resulted in an increase in [Ca2+]i from 74 +/- 5 to 219 +/- 8 nM and myogenic constriction. Application of Indo-V (0.01-3 microM) or DOG (0.1-30 microM) induced constriction and decreased [Ca2+]i to 140 +/- 11 and 127 +/- 12 nM, respectively, at the highest concentrations used. In the presence of Indo-V, the dihydropyridine Ca2+-channel-blocker nisoldipine produced nearly maximum dilation and decreased [Ca2+]i to 97 +/- 7 nM. In alpha-toxin-permeabilized arteries, the constrictor effects of Indo-V and DOG were not observed in the absence of Ca2+. Both PKC activators significantly increased the degree of constriction of permeabilized arteries at different [Ca2+]i. We conclude that 1) Indo-V- or DOG-induced constriction of pressurized arteries requires Ca2+ influx through voltage-dependent Ca2+ channels, and 2) PKC-induced constriction of pressurized rat cerebral arteries is associated with a decrease in [Ca2+]i, suggesting an increase in the Ca2+ sensitivity of the contractile process.

Numerical modeling of the constriction of the dc positive column in rare gases

The constriction of the positive column of a dc glow discharge in argon at high pressures is analyzed using the continuity equations for the charged particles and the gas thermal balance equation coupled with the local electron Boltzmann equation and a detailed collisional-radiative model for the atomic and ionic species. Contrary to the other existing models of the constriction in inert gas, the present model is self-consistent and fully detailed, and provides a quantitative description of all the discharge properties. The numerical techniques used to solve the boundary value problem corresponding to our set of equations are discussed in detail. The transition from the diffuse to the constricted state and the properties of this latter state are investigated. The model predicts the existence of multimodal solutions for the discharge parameters as a function of the discharge specific power, within a limited range of values of the latter above a critical value, which explains the observed abrupt changes in the discharge parameters and the hysteresis associated with constriction. The radial distributions of the gas temperature and of the densities of all neutral and charged species considered are determined along with various other discharge characteristics, such as the steady-state discharge maintenance electric field, as a function of the discharge operating parameters. The results for argon show satisfactory agreement with data from experiments. A few model simulations are further presented that enable one to gain physical insight on the relevant kinetic processes of constriction in argon. Such simulations are instrumental to understanding also the mechanisms of constriction in the other inert gases.

Receptor mechanisms of serotonin-induced prenodal lymphatic constriction in the canine forelimb.

Numerous endogenous vasoactive agents have been shown to cause lymphatic smooth muscle contraction. In this study, we assessed the ability of serotonin (5-HT) to alter lymphatic smooth muscle activity and elucidated the receptor mechanisms of 5-HT's actions. Both intralymphatic and intra-arterial administration of 5-HT significantly increased lymphatic smooth muscle activity in lymphatics perfused at constant flow, as indicated by an increase in lymphatic perfusion pressure. The 5-HT-induced increase in lymphatic perfusion pressure is attenuated but not blocked by the intra-arterial infusion of phentolamine, suggesting the involvement of alpha-adrenoreceptors and 5-HT receptors. Intralymphatic infusion of the 5-HT2-receptor-agonist alpha-methylserotonin significantly increased lymphatic perfusion pressure, either alone or when administered into an alpha-receptor blocked preparation, whereas the 5-HT1-receptor-agonist carboxyami-dotryptamine maleate did not effect the prenodal lymphatics. These data indicate that the lymphatic smooth muscle contraction produced by 5-HT is mediated both by lymphatic alpha-adrenoreceptors and 5-HT2 receptors.

Mechanism of drop constriction in a drop-on-demand inkjet system

In this paper, results of an investigation on the process of drop formation in piezo‐electrically driven drop‐on‐demand inkjet systems are presented. The focus is on theoretical hydrodynamical aspects of the process with special attention to drop constriction. It is shown that the inception of drop constriction has its origin in acceleration forces in contrast to the well‐known phenomena in the field of interfacial instability such as pendant drop, end pinching and capillary wave break‐up. Some results from computer simulations and from experimental investigations are also added to illustrate relevant processes preceding and following drop constriction.

Bacterial cell division.

Bacteria usually divide by building a central septum across the middle of the cell. This review focuses on recent results indicating that the tubulin-like FtsZ protein plays a central role in cytokinesis as a major component of a contractile cytoskeleton. Assembly of this cytoskeletal element abutting the membrane is a key point for regulation. The characterization of FtsZ homologues in Mycoplasmas, Archaea, and chloroplasts implies that the constriction mechanism is conserved and that FtsZ can constrict in the absence of peptidoglycan synthesis. In most Eubacteria, the internal cytoskeleton must also regulate synthesis of septal peptidoglycan. The Escherichia coli septum-specific penicillin-binding protein 3 (PBP3) forms a complex with other enzymes involved in murein metabolism, suggesting a centrally located transmembrane complex capable of splicing multiple new strands of peptidoglycan into the cell wall. Important questions remain about the spatial and temporal control of bacterial division.

Intracellular mechanisms of constriction of rat aorta by ethanol

The intracellular mechanisms mediating vasoconstriction by ethanol are poorly understood. This investigation was designed to provide evidence on the role of protein kinase C (PKC) and calmodulin in vasoconstriction by ethanol. We studied helically cut strips of rat aorta that were exposed to ethanol before and in the presence of the PKC inhibitors calphostin C (79, 239, and 798 nM) or 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7, 10 μM), and the calmodulin inhibitor, trifluoperazine (TFP, 10 μM). To test for the specificity of the PKC inhibitors, we measured the responses of aortas to potassium and phorbol 12-myristate 13-acetate (PMA) in the absence and presence of calphostin C and H7. To test for the specificity of TFP, we measured the responses of aortas to serotonin, potassium, PMA, and the thromboxane A 2 mimic, 9,11-dideoxy-11α,9α-epoxy-methanoprostaglandin F 2α (U46619), in the absence and presence of TFP. We also studied the effect of the combination of calphostin C and TFP on constriction of the aorta by ethanol. We also measured the importance of intracellular and extracellular calcium in constriction of the aorta by ethanol. Force generation was measured before, and then during exposure of the strips to calcium-free buffer with EGTA, or calcium-free buffer with EGTA plus caffeine. We found that both PKC inhibitors antagonized vasoconstriction by ethanol and PMA. However, H7 antagonized contractions by potassium, but calphostin C did not. We found that TFP caused 99 ± 1% inhibition of maximum contraction to serotonin, 90 ± 4% inhibition of maximum contraction to potassium, 63 ± 6% inhibition of maximum contraction to PMA, and 8 ± 5% inhibition of maximum contraction to U46619. TFP caused a 22 ± 8% inhibition of contraction to ethanol. The combination of TFP and calphostin C antagonized vasoconstriction by ethanol to a degree similar to that of calphostin C alone. We also found that contractions to ethanol were only 16 ± 7% of control values in a calcium-free plus EGTA buffer. Contractions to ethanol were 0 ± 1% of control values in calcium-free buffer wtih EGTA plus caffeine. We conclude that: 1 — vasoconstriction by ethanol is, at least in part, mediated by PKC; 2—constriction by ethanol is mediated to a minimal extent by calmodulin, and 3—part of the constriction by ethanol of the aorta is mediated by a caffeine-sensitive pool of intracellular calcium.

Mechanism of Acetylcholine-Induced Constriction Enhanced by Endothelial Removal in Isolated, Perfused Canine Basilar Arteries

We examined the responses to intraluminally applied acetylcholine (ACh) in isolated and perfused canine basilar arteries by the stainless-steel cannula-inserting method. In control vessels with intact endothelium, ACh produced a slight vasodilatation followed by a long-lasting vasoconstriction in the absence of induced tone. Propranolol, a beta-adrenoceptor blocker, had no effect on the response to ACh. After endothelial removal with intraluminal saponin, the constrictor component of the response to ACh was significantly enhanced, and the constrictions to prostaglandin F2 alpha (PGF2 alpha) and potassium chloride (KCl) were significantly potentiated. After exposure to extraluminal oxyhemoglobin, the ACh-induced constriction was significantly augmented, whereas the dilator component of the response to calcium ionophore A23187 was significantly attenuated. The enhanced constriction to ACh after endothelial removal was significantly blocked by OKY-046 (a thromboxane synthetase inhibitor) and nimodipine (a dihydropyridine calcium antagonist), but was slightly though not significantly suppressed by AA-861 (a lipoxygenase inhibitor). The response to PGF2 alpha was not altered by OKY-046 or AA-861. These results suggest that the potentiation of ACh-induced constriction after endothelial removal may be mediated in part by thromboxane A2 (TXA2), linked with extracellular calcium entry in smooth muscle cells (SMC). This mechanism might be involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH).

Can Transcutaneous Oximetry Detect Nutritive Perfusion Disturbances in Patients with Lower Limb Ischemia?

Transcutaneous oximetry (Tc pO 2) performed at 37 and 44° on the dorsum of the foot and capillary microscopy of the nailfold of the big toe were applied to 85 patients with various (including asymptomatic) stages of lower limb ischemia to appreciate the relationship between (disturbances in) capillary perfusion and skin oxygen tension. In mildly diseased patients, capillary perfusion as measured by direct observation, was preserved. In critically ischemic patients in the supine position, red blood cell-perfused capillary density was reduced. Nutritive perfusion was severely reduced and showed an absent reactive hyperemia after a 1-min arterial occlusion. Also, postural vasoconstrictive activity was reduced, Tc pO 2 measured at 37° was very low already in mildly diseased patients, illustrating the poor oxygen diffusion toward the skin. At 44°, Tc pO 2 was severely reduced in critically ischemic patients. Reactive hyperemic response and postural vasoconstriction were suppressed, due to local heating of the skin. Measurement of the Tc pO 2 has limitations in the assessment of nutritive perfusion, as opposed to capillary microscopy, since it is an indirect measure of skin perfusion, not necessarily derived from capillaries only. The obligatory local skin heating impairs physiological studies as to hyperemic reserve capacity or postural constriction mechanisms. Thus, transcutaneous oximetry is a poor method of characterizing pathophysiological mechanisms occurring in skin nutritive microcirculation. However, capillary microscopy and transcutaneous oximetry can give additive information as to the severity of peripheral ischemia. Peak red blood cell velocity during reactive hyperemia using capillary microscopy and the resting Tc pO 2 at 44°, both measured in the supine position, appeared to be valuable microcirculatory parameters in detecting critical limb ischemia.

Ultrastructure of an extreme thermophilic hydrogen-oxidizing bacterium Calderobacterium hydrogenophilum

Calderobacterium hydrogenophilum is an extreme thermophilic, obligately chemoautotrophic, hydrogen-oxidizing bacterium. The cells were shown to be nonmotile straight rods of average size 0.4x2.5 μm. After negative-staining of the whole cells, no flagella were observed. The multilayered cell wall was of type 1 and possessed a crystalline proteinaceous surface layer exhibiting p4 symmetry. The square unit cells had a lattice constant of approximately 11 nm. Cell division occurred by a constriction mechanism. C. hydrogenophilum differred from a similar hydrogen-oxidizing eubacterium, Hydrogenobacter thermophilus, by the absence of intracytoplasmic membrane structures in chemically fixed cells. However, an electron-dense intracytoplasmic hemispherical structure adhering to the inner membrane was frequently observed.

Histochemistry and immunohistochemistry of extracellular matrix of rat fetal Ductus arteriosus during the indomethacin-induced constriction.

Administration of anti-inflammatory non-steroidal drugs to pregnant animals causes constriction of the fetal ductus arteriosus (DA). To clarify the mechanism of the indomethacin-induced constriction of the rat fetal DA, extracellular matrix (ECM) components were observed by immunohistochemical techniques with antibodies 2B1, 6B6, 3B3, 9A2 and others to various kinds of proteoglycans (PGs). In the 10mg/kg group, the large PG revealed with antibody 2B1 was increased in the inner and outer media at constriction, and chondroitin 6-sulfate PG was strongly immunostained with antibody 3B3 as granular substances in the outer media, although no difference in stainability of chondroitin 4-sulfate PG revealed with the antibody 9A2 was observed between experimental and control groups. This suggests that the cells composing the fetal DA showed a tendency of proliferation and resultant production and aggregation of large PG with chondroitin 6-sulfate chains during constriction induced by indomethacin-treatment.

Importance of prostanoids in calcium chelator-induced airway constriction

To elucidate the mechanism of calcium chelator-induced airway constriction, we examined the relationship between prostanoids and histamine in bronchoalveolar lavage (BAL) fluid and the magnitude of airway constriction in peripheral airways of anesthetized Basenji-Greyhound dogs. A wedged bronchoscope technique was used to measure collateral system resistance (Rcs) before and after aerosol challenges. Sublobar segments were challenged either with acetylcholine or with Na2EDTA in the presence or absence of meclofenamate sodium (3 mg/kg iv) or methylprednisolone (2 mg.kg-1.day-1). After measurements of Rcs, BAL was performed, and the fluid was analyzed for prostanoids with the use of gas chromatography-mass spectrometry. Sublobar segments challenged with Na2EDTA showed increased concentrations of prostaglandin (PG) D2 but no increases in PGE2, PGF2 alpha, 9 alpha,11 beta-PGF2, 6-keto-PGF1 alpha, thromboxane B2, or histamine. There was a strong relationship (r = 0.84, P = 0.005) between changes in Rcs after Na2EDTA and concentrations of PGD2 in BAL fluid. Acetylcholine, which increased Rcs to a similar degree as Na2EDTA did, produced no significant increase in prostanoid concentrations. Changes in Rcs after Na2EDTA and concentrations of PGD2 were reduced in the presence of meclofenamate or methylprednisolone. These data support the idea that the mechanism of calcium chelator-induced bronchoconstriction involves the release of bronchoconstricting prostanoids.

KCl and angiotensin responses in isolated rat renal arterioles: effects of diltiazem and low-calcium medium.

Studies in intact renovascular models have shown that calcium entry blockers inhibit angiotensin (ANG II)-induced vasoconstriction in afferent (AA) but not efferent arterioles (EA), suggesting that increases in smooth muscle cell cytosolic calcium, the initiating intracellular message, result from entry through potential-operated channels in AA, but from organelle storage mobilization or entry through nonpotential-operated channels in EA. The present study examined the effects of diltiazem (10(-5) M) on the constrictor responses to KCl (50 mM) and half-maximal constricting concentrations (EC50) of ANG II and the effects of low-calcium bathing medium on EC50 ANG II responses in isolated rat AA and EA. KCl caused slightly greater decreases in lumen diameter in AA than in EA (P < 0.05) that were completely inhibited by diltiazem in both. Vasoconstriction to ANG II was significantly inhibited by diltiazem (29 +/- 12 vs. 67 +/- 31%; P < 0.02) in AA. However, constrictor response to ANG II in EA was unchanged by diltiazem (42 +/- 32 vs. 41 +/- 31%). Constriction to ANG II of AA in low-calcium medium was significantly attenuated (8 +/- 13 vs. 54 +/- 12%; P < 0.01); however, EA constrictor response was not affected (43 +/- 22 vs. 51 +/- 19%). These data indicate that EC50 ANG II-induced AA constriction requires calcium entry primarily through potential-operated channels. While potential-operated calcium entry channels can be functionally expressed in EA, intracellular calcium mobilization is the primary mechanism for ANG II-induced constriction.

Pial arteriolar constriction following cortical spreading depression is mediated by prostanoids

The mechanism of pial arteriolar constriction during post-cortical spreading depression (CSD) was examined in anesthetized adult rabbits. Using a closed cranial window and intravital microscopy, the diameter of a pial arteriole was determined. A single CSD was induced by KCl micro-injection and its propagation was monitored by recording slow potential changes accompanying CSD. Prostanoid levels in cortical cerebrospinal fluid (CSF) were determined by radioimmunoassay. Pial arteriolar diameter increased significantly from 76 ± 6 to a maximum of 119 ± 5 μm(57%, n = 8) for 1.6 ± 0.1 min when CSD (velocity, 2.8 ± 0.1mm/min) reached the cortex just beneath the vessel irrespective of its location. Shortly after CSD expiration from the cortex, pial arteriolar diameter decreased from the pre-CSD level to a minimum of 67 ± 5 μm(12%, n = 8) for 19.5 ± 2.1 min. CSD was elicited again in the same animal while the cortical surface under the window was continuously superfused with artificial CSF at a flow rate of 3.2–4.5 ml/min. Pial arteriolar dilation (from75 ± 6to115 ± 3 μm, 53 ± 9%,for1.6 ± 0.1min, n = 8) was observed again during CSD (velocity,2.7 ± 0.2mm/min), however, no constriction of the vessel was seen after CSD expiration. Indomethacin pretreatment ( n = 11) to inhibit prostanoid production enhanced the magnitude of CSD-induced vasodilation from the pretreatment levels of59 ± 9% (from 82 ± 5to130 ± 8 μm for1.7min) to the post-treatment levels of 82 ± 13% (from 78 ± 5to142 ± 12 μm for1.8min). In contrast, the post-CDS vasoconstriction observed before indomethacin (11 ± 2% for 16.6 ± 2min) was completely ablated after indomethacin. CSF prostanoids (pg/ml, n = 11) increased during the CSD-induced vasodilation from 1429 ± 100 to 2889 ± 283 (102%) for prostaglandin E 2 (PGE 2), from 1453 ± 106to1945 ± 138 (34%) for 6-keto-PGF 1α, and from 3506 ± 390to6777 ± 745 (93%) for PGF 2α. Throm☐ane B 2 (TXB 2) did not increase significantly. CSF prostanoids increased further during the post-CSD vasoconstriction; PGE 2, 213% ( n = 8); 6-keto-PGF 1α, 99% ( n = 7); PGF 2α, 236% ( n = 8) and TXB 2, 56% ( n = 6). Indomethacin decreased the resting levels of all the prostanoids and blocked their increases during the CSD-induced vasodilation and during the post-CSD period. These results suggest that while prostanoids attenuate pial arteriolar dilation during CSD, they mediate the post-CSD constriction of the vessel.

Oxygen-mediated regulation of neonatal and adult rabbit aortic tension.

To determine the influence of oxygen on aortic tension in young and mature animals, we evaluated the response of neonatal and adult rabbit aortic rings to changes in oxygen tension. In 95% nitrogen/5% carbon dioxide, endothelium-derived nitric oxide was not a factor in the development or maintenance of low resting aortic ring tensions. However, the production of endothelium-derived nitric oxide increased in 21% oxygen/74% nitrogen/5% carbon dioxide and 95% oxygen/5% carbon dioxide, and attenuated a concomitant endothelium-independent mechanism of increasing vascular tension. A protein kinase inhibitor, 0.2 mM 1-(5-isoquinolinyl-sulfonyl)-2-methyl piperazine (H-7) inhibited oxygen-mediated constriction of neonatal vessels, but also significantly reduced the contractile response to 60 mM KCl. In conclusion, resting aortic tension is in part determined by oxygen-mediated control of the production of endothelium-derived nitric oxide and one or more opposing endothelium-independent mechanisms of constriction.

Inhibitory reflex during bronchoconstrictions induced by histamine and Ascaris suum antigen.

We investigated the involvements of sympathetic and nonadrenergic nervous systems in the inhibitory reflex following bronchoconstriction in dogs. Inhalations of a 0.00125% solution of histamine and Ascaris suum antigen (3 mg protein) to the bronchial side induced reflex tracheal constriction following bronchoconstriction. An intra-arterial infusion of 5 micrograms/min of atropine to the tracheal site changed the reflex tracheal constrictions by histamine and antigen inhalations into tracheal dilatations. The reflex tracheal dilatations were abolished by the combination of intra-arterial propranolol (100 micrograms) and transections of both the bilateral superior laryngeal nerves and the spinal cord at the C1 level. The reflex tracheal constrictions induced by histamine and antigen inhalations were increased with 100 micrograms propranolol. Furthermore, the reflex tracheal constrictions were enhanced by the combination of 100 micrograms propranolol and transection of the spinal cord. These findings indicate that during the constriction of the bronchial smooth muscle, not only a reflex tracheal constriction mechanism but also one of reflex dilatation operates and that the latter reflex response may be mainly mediated by the sympathetic nerves, with partial involvement of the nonadrenergic nerves. This inhibitory reflex may attenuate asthmatic bronchoconstriction.

Inhibitory Reflex during Bronchoconstrictions Induced by Histamine and Ascaris Suum Antigen

We investigated the involvements of sympathetic and nonadrenergic nervous systems in the inhibitory reflex following bronchoconstriction in dogs. Inhalations of a 0.00125% solution of histamine and Ascaris suum antigen (3 mg protein) to the bronchial side induced reflex tracheal constriction following bronchoconstriction. An intra-arterial infusion of 5 μg/min of atropine to the tracheal site changed the reflex tracheal constrictions by histamine and antigen inhalations into tracheal dilatations. The reflex tracheal dilatations were abolished by the combination of intra-arterial propranolol (100 μg) and transections of both the bilateral superior laryngeal nerves and the spinal cord at the C1 level. The reflex tracheal constrictions induced by histamine and antigen inhalations were increased with 100 μg propranolol. Furthermore, the reflex tracheal constrictions were enhanced by the combination of 100 μg propranolol and transection of the spinal cord. These findings indicate that during the constriction of the bronchial smooth muscle, not only a reflex tracheal constriction mechanism but also one of reflex dilatation operates and that the latter reflex response may be mainly mediated by the sympathetic nerves, with partial involvement of the nonadrenergic nerves. This inhibitory reflex may attenuate asthmatic bronchoconstriction.

Functional antagonism of airway constriction in the canine lung periphery.

We studied the ability of a beta-adrenergic agonist (albuterol) to attenuate calcium chelator- and acetylcholine-induced airway constriction in the lung periphery of anesthetized mongrel and Basenji-Greyhound (BG) dogs. A wedged bronchoscope technique was used to measure collateral system resistance before and after challenges with aerosolized Na2EDTA and acetylcholine. Time course of the response to Na2EDTA differed significantly between mongrel and BG dogs. Peak response to challenge with 4% Na2EDTA occurred within 2 min for mongrel dogs and at 5 min for BG dogs. Albuterol (1 microgram/kg iv) significantly attenuated Na2EDTA-induced bronchoconstriction in both groups of animals (P less than 0.01, each group). Albuterol (1 microgram/kg iv) significantly attenuated acetylcholine-induced bronchoconstriction in mongrel (P less than 0.01) but not in BG dogs. We conclude that a qualitative difference exists in the mechanism of Na2EDTA-induced constriction in the lung periphery of BG compared with mongrel dogs. In addition, the lung periphery of BG dogs demonstrates reduced beta-adrenergic sensitivity with respect to a cholinergic challenge compared with mongrels, suggesting enhanced cholinergic inhibition of the beta-adrenergic system.

Effects of PAF on isolated rat airways perfused with blood-free solution

We examined the mechanism of constriction and muscarinic augmentation of contraction of airway smooth muscle caused by platelet-activating factor (PAF) in airways from 55 Sprague-Dawley rats perfused through the isolated bronchial circulation (BC) and pulmonary circulation (PC) and isometrically in tissue perfusion chambers. Dose-response curves were generated cumulatively by infusing 10(-10) to 10(-7) mol PAF dissolved in Krebs-Henseleit solution buffer containing 4% bovine serum albumin into the BC or PC. The efficacy of PAF in central airways (BC) was approximately twofold greater in increasing lung resistance (RL) than for more peripheral airways perfused by the PC (P less than 0.05). Tachyphylaxis was demonstrated in both BC and PC for preparations in which a second PAF dose-response curve was generated. Bolus injection of 10(-6) mol of the PAF antagonist, CV-6209, plus 10(-7) mol PAF caused 81% reversal of the maximal BC response. The same dose of CV-6209 reversed the response to PAF in the PC by 99.2%. Initial administration of 10(-6) mol CV-6209 with PAF prevented completely contraction elicited by PAF in the BC and PC. Concentration-response studies also were generated isometrically in tissue perfusion chambers from 64 tracheal smooth muscle strips. Maximal contraction elicited by 10(-6) M PAF was blocked completely with 10(-6) M CV-6209. In separate studies, addition of 10(-6) mol CV-6209 to the BC perfusate caused 93% blockade of the RL response to PAF and 100% inhibition when administered in the PC. Prior administration of PAF caused two- to fourfold augmentation of the contractile response to acetylcholine (ACh) within the same preparation; in the presence of CV-6209, the response to ACh was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of diltiazem and thromboxane A 2 synthetase inhibitor (OKY-046) on vessels following experimental subarachnoid hemorrhage

In order to examine the functional changes in the vascular smooth muscle, the effects of a thromboxane A 2 synthetase inhibitor (OKY-046) and a calcium channel blocker (diltiazem) on vessels following subarachnoid hemorrhage, and the contractile activity of cerebral vessels with various vasoactive agents, were investigated by studying isometric tension recordings in rings of cat basilar artery. The maximum contractile activities of the vessels in response to noradrenalin and adrenaline during the course of subarachnoid hemorrhage were significantly less than those in the control group. On the other hand, the maximum contractile activity of the vessels in response to prostaglandin F 2α on the seventh day following subarachnoid hemorrhage was significantly augmented compared with that in the control group. A significant decline in the relaxation of responsiveness to diltiazem during the course of subarachnoid hemorrhage was observed compared with that of diltiazem in the control group. This responsiveness to vasoactive agents was not influenced by the application of OKY-046. The present study reveals functional changes in vascular smooth muscle exposed to subarachnoid hemorrhage in response to vasoactive agents and a calcium entry blocker. Thromboxane A 2 may not be a significantly influential factor in the present results. It is suggested that cerebral vasospasm may well be related to functional changes of the arterial wall, which appear to be associated with derangement of the mechanisms of smooth muscle constriction and dilatation based on organic changes.