Artery Of Dogs Research Articles

Limitation of infarct size with preconditioning and calcium antagonist (Diltiazem): Difference in99mTc-PYP uptake in the myocardium

Ischemic cell injury and the uptake mechanism of 99mTc-PYP (Pyrophosphate) were studied with preconditioning and calcium antagonist. The coronary artery of an adult mongrel dog was clamped for 1 hour, followed by reperfusion and 99mTc-PYP injection. A control group (group C, n = 8), a group in which continuous drip infusion of diltiazem (10 mg/kg) (group D, n = 7), and a group preconditioned by six 5-minute clampings and perfusions before occlusion (group P, n = 6) were compared. Wall motion was fully recovered in group D but not in group P after 2 hours of reperfusion. The 99mTc-PYP uptake ratio showed a significant (p < 0.05) reduction in group D (11.5 : 3.6 compared with group C), but not in group P (11.5 : 9.1, p = 0.25). The infarct area was 1.2 +/- 0.6% of the left ventricle in group D, 1.3 +/- 0.4 in group P, and 6.4 +/- 1.0 in group C (p < 0.01 in groups D and P vs. group C). These findings suggest that preconditioning does not alleviate stunning, but it improves cell injury in spite of high uptake of 99mTc-PYP. Diltiazem protects from both stunning and cell injury, suggesting a different mechanism of myocardial protection from that of preconditioning.

Airway circulation in health and disease.

The third biennial meeting of the da Vinci Society for the Study of the Circulation was held at the University of Bordeaux, France, from September 12‐14, 1995. There were 44 participants from nine different countries. The topic of the meeting was Airway Circulation in Health and Disease: Interaction between Vasculature and Pulmonary Smooth Muscles. Thirty one presentations were given and these were followed by lively discussions. Guest speaker, Paul Vanhoutte, gave a stimulating talk entitled Epithelium, Endothelium and Smooth Muscles in Walls. Old topics that had been at the forefront some decades ago were revisited and new insights into the physiology and pathophysiology of the airway circulation were discussed. Haemodynamics of the airway circulation The site of anastomoses between the bronchial and the pulmonary circulation is still the subject of debate. Striking angiogenesis of the airway circulation and medial hypertrophy of small pulmonary arteries have been observed 4 months after ligation of the left pulmonary artery in dogs. Using the sudden occlusion technique to measure pre- and postcapillary pulmonary vascular resistance in the in situ perfused left lower lobe of dogs, R. Michel was able to localize anastomoses between the bronchial and the pulmonary circulations at the precapillary level. There may be similarities between these findings and those from a study performed by D. Schraufnagel in rats. The rats, made cirrhotic by ligation of the bile duct, developed a striking increase of the vasa vasorum of the pulmonary arteries, as demonstrated by use of plastic casting. P. Pare has also investigated the extent of these anastomoses in open-chested, anaesthetized sheep. Radiolabelled red blood cells were injected into the common bronchial artery of sheep, whilst blood samples were obtained simultaneously from the aorta, the left ventricle, inferior vena cava and the right ventricle; this is a revival of the classical single-injection, multiple-sampling indicator-dilution method. The timing and the area under the indicator dilution curves were calculated. The results showed that at least 80% of the venous return from the bronchial circulation drained to the left side of the heart, whereas less than 20% returned to the right heart. In additional studies, Pare also examined the extraction of labelled polymorphonuclear leucocytes (PMNs) injected directly into the pulmonary or the bronchial artery. First-pass extraction of the PMNs was much lower in the bronchial compared to the pulmonary circulation (50 vs 80‐90%), suggesting that some of the anastomoses between the bronchial and the pulmonary vasculature were at the postcapillary level. In summary, results from the dogs and rats demonstrated considerable remodelling of the bronchial circulation and evidence for precapillary anastomoses; whereas, in the acute study in normal sheep, at least some of the anastomoses were postcapillary. At this stage, it does not seem possible to decide whether this is due to species differences or to the effects of angiogenetic remodelling of the bronchial circulation in some studies.

Role of nitric oxide in the anti-thrombogenic response to norepinerphrine in the coronary artery of dogs

Role of nitric oxide in the anti-thrombogenic response to norepinerphrine in the coronary artery of dogs

Vasodilation by intrathecal lipopolysaccharide of the cerebral arteries after subarachnoid haemorrhage in dogs.

To investigate the influence of inducible nitric oxide synthase on cerebral arteries after subarachnoid haemorrhage (SAH) in vivo, lipopolysaccharide (LPS), a major inducer of inducible nitric oxide synthase, was injected intracisternally into control and SAH model dogs. Intracisternal injection of LPS (0.5 mg) produced a long-lasting, submaximal vasodilation of the basilar artery of control dogs on angiography. This effect became significant at 4 hours after LPS injection and plateaued after 6 hours. This vasodilation was reduced by N(G)-monomethyl-L-arginine. Vasopressin slightly suppressed the vasodilation, while bradykinin increased it. The concentration of L-arginine in CSF decreased after LPS injection, while that of L-citrulline increased. In cytokines, the concentration of tumour necrosis factor-alpha; (TNF-alpha;) in CSF increased transiently at 4 hours after LPS injection, while interleukin-1 beta, interleukin-6, interferon-gamma, did not change. These data suggest that vasodilation by LPS is mainly due to nitric oxide predominantly synthesized by an inducible nitric oxide synthase, proximally induced by TNF-alpha. Our data make it unlikely that SAH itself induces the inducible nitric oxide synthase in vascular tissue, since isolated endothelium-denuded basilar artery from SAH model dogs did not respond to L-arginine. In SAH model dogs, the degree of vasodilation by LPS differed with the severity of vasospasm. Vasodilation was much greater in mild than in severe vasospasm in dogs, and was increased by superoxide dismutase. These findings suggest that the induction of inducible nitric oxide synthase or its activity may be less effective in severe vasospasm.

Enhanced coronary vasoconstriction to endothelin-B-receptor activation in experimental congestive heart failure.

Endothelin (ET), a coronary vasoconstrictor, mediates its activity through the specific receptors ET-A and ET-B, which may demonstrate different activity under pathophysiological conditions. Thoracic inferior vena cava constriction (TIVCC) is an experimental model of congestive heart failure that is characterized by a decrease in cardiac output and an increase in circulating ET concentrations. The present study was designed to test the hypothesis that experimental heart failure altered coronary vascular responsiveness to ET-A- and ET-B-receptor stimulation in vivo. ET-1 was infused at a rate of 2 ng/kg per minute into the left circumflex coronary artery in normal dogs (n = 5) and in dogs subjected to TIVCC (TIVCC dogs, n = 6). Similarly, sarafotoxin, an ET-B-receptor agonist, was infused at the same dosage in normal (n = 5) and TIVCC (n = 6) dogs. Intracoronary infusion of ET-1 significantly decreased coronary blood flow and increased coronary vascular resistance in normal dogs; this effect was significantly attenuated in TIVCC compared with normal dogs. The percent changes in coronary blood flow and coronary vascular resistance in the TIVCC compared with the normal dogs was -11 +/- 8% versus -48 +/- 7% (P < .01) and 29 +/- 10% versus 105 +/- 23% (P < .01), respectively. There was no significant effect on coronary blood flow, coronary vascular resistance, or coronary artery diameter in normal dogs that received an intracoronary infusion of sarafotoxin. In contrast, the administration of intracoronary sarafotoxin in TIVCC compared with normal dogs resulted in significant percent changes in coronary blood flow and coronary vascular resistance (-31 +/- 4% versus -7 +/- 3% [P < .001] and 53 +/- 12% versus 12 +/- 8% [P < .02], respectively). The present study demonstrates an attenuated coronary vasoconstrictor response to ET-1 with an enhanced vasoconstrictor response to sarafotoxin and suggests an alteration in coronary ET receptor sensitivity in experimental heart failure.

Burn Edema Reduction by Methysergide Is Not Due to Control of Regional Vasodilation

To determine the extent to which edema modulation by methysergide is due to a blunting of the regional vasodilator response to scald and/or local reduction of transvascular fluid flux, a canine hind limb lymphatic was cannulated. Femoral blood flow (Qa; ml/min), lymph flow (QL; μl/min/100 g), and lymph-to-plasma protein ratios (CL/CP) were monitored in groups of five dogs before and 4 hr after 5-sec, 100°C foot paw scald; high (1.0 mg/kg) or low (.5 mg/kg) dose of methysergide 30 min before scald. The compression on a clamp placed around the femoral artery in other dogs was adjusted after scald to simulate the blunting effect on Qaobserved in methysergide treated dogs. Hind leg venous pressure was elevated to ≈40 mm Hg before experimentation until steady state QLand (CL/CP)minwere reached. Protein reflection coefficient (σd; 1 − CL/CP) and fluid filtration coefficient (Kf) were calculated. Compared to preburn values, all groups showed significant (P< 0.002, analysis of variance) increases in CL/CPand Kf. Contrasted with the burn only group, methysergide blunted increases in Qa, Kfand paw weight gain in a dose-dependent fashion, with no effect on the reflection coefficient. Compression clamp control of femoral Qacaused no effects on permeability. Methysergide limits burn edema in a dose-related fashion, though not due to a blunting of the regional vasodilator response. Local, not regional, mechanism(s) likely mediate this response.

The Effects of Hypoxic Stimulation of Neuroepithelial Bodies on the Respiratory Pattern of Peripheral Chemoreceptor-Denervated Dogs

This study was carried out with the purpose of investigating the functional significance and the role of neuroepithelial bodies (NEB) in the regulation of respiration in hypoxia. 22 mongrel dogs of 17-23 kg. in body weight were used as experimental animals. The animals were anesthetized with intravenous injections of sodium pentobarbital (30 mg/kg). The carotid and aortic chemoreceptors of one dog (the recipient) were denervated. By means of a cross circulation technique, the cerebral circulation of the recipient dog was separated from its systemic circulation and was perfused via the vertebral and internal carotid arteries with blood from the common carotid artery of a donor dog. 0n the breathing of the normoxic and hypoxic gast mixtures by the recipient animal, its respiratory parameters and systemic arterial blod pressure were recorded. At the end of each experimental phase, Pa02, PaCO2 and pHa were determined in blood samples obtained from the vertebral and femoral arteries. 0n the breathing of the hypoxic gas mixture (7% 02-93% N2) by the recipient dog (cerebral normoxia-systemic hypoxia), tidal volume (VT), respiratory frequency [f(min-1)] and ventilation minute volume (VE) were significantly increased to 27.6 %, 32% and 30.1 %, respectively, of the normoxic values as 100. These respiratory responses were followed by and apneic phase. Following biiateral vagotomy in the chemoreceptor-denervated recipient dog, the respiratory responses to hypoxia were diminished. The hypoxic stage was again followed by an apneic phase. Upon the induction of cerebral hypoxia-systemic hypoxia in the recipient animal, significant diminutions in VT were accompanied by a significant increase in [f(min-1)] when compared wtih the control normoxic values. An apneic phase again followed this last experimental stage. ln conclusion, the results of the present study suggest that in cerebral normoxic-sytemic hypoxic phase the increase in respiratory activity of peripheral chemorecteptor-denervated dogs may be attributed to the effect of facilitatory impulses from the NEB, transmitted to respiratory centers via the vagal fiber. In cerebral hypoxia, on the other hand, the decrease in neuronal activity of the centers may overcome the effects of the facilitatory impulses from the NEB.

Does inhibition of coronary nitric oxide synthesis alter coronary vascular tone in normal dogs?

To examine whether endothelial nitric oxide formation contributes to the vascular tone of resistance coronary vessels in vivo, we administered NG-nitro-L-arginine methyl ester (L-NAME) (10 and 100 micrograms/kg/min), a nitric oxide synthase inhibitor, as well as D-enantiomer into the left circumflex artery in normal dogs. Intracoronary L-NAME, which was associated with dose-related reductions in acetylcholine-induced coronary vasodilation, significantly reduced the baseline left circumflex blood flow by 6% and increased coronary vascular resistance of the left circumflex artery by 6%. D-enantiomer was ineffective in altering baseline coronary blood flow and vascular resistance of the left circumflex artery. These results indicate that continuous nitric oxide formation in the vasculature is important in the regulation of the coronary vascular tone of resistance vessels in vivo, and serves to maintain the vessels in a dilated state.

Vascular smooth muscle reactivity and endothelium derived relaxing factor in experimental obstructive jaundice.

Obstructive jaundice is associated with a predisposition to systemic hypotension and acute renal failure. Altered vascular reactivity may contribute to the development of hypotension. In this experimental study on dogs, alterations in vascular contractile responses to noradrenaline, serotonin and KCl were investigated. Contractile responses to noradrenaline, serotonin,,, KCL and relaxation responses to papaverin and acetylcholine were provoked in isolated femoral arteries of both control dogs and animals with obstructive jaundice. In this situation concentration-response curves of noradrenaline and serotonin were blunted when compared with controls. This blunting disappeared when endothelium was removed. In rings precontracted with phenylephrine, EDRF relaxation responses to acetylcholine were increased significantly as compared to controls: at lower concentrations maximal relaxation response occurred. Contractile responses to KCl and relaxation responses to papaverin did not differ between the groups, endothelium present or removed. These results indicate that obstructive jaundice induces a decrease in vascular contractile responses and an increased EDRF relaxation response. We suggest that an excess in the amount of released EDRF may be one of the causes inducing systemic hypotension in obstructive jaundice.

Cardioprotection due to preconditioning correlates with increased ecto-5'-nucleotidase activity.

We investigated whether loss of myocardial protection after ischemic preconditioning (IP) is related to the extent of deactivation of activated ecto-5'-nucleotidase. The coronary arteries of mongrel dogs were occluded four times for 5 min separated by 5 min of reperfusion (IP). Five (IP1), 30 (IP2), 60 (IP3), and 120 min (IP4) after the fourth 5-min coronary occlusion or after a corresponding nonischemic period (control groups), the coronary arteries were occluded for 90 min followed by 6 h of reperfusion. The infarct size-limited effect of IP gradually disappeared in the IP2 (21.6 +/- 3.9%) and IP3 (33.8 +/- 3.6%) groups compared with the IP1 group (8.3 +/- 1.6%) and returned to the control level in the IP4 group (39.9 +/- 5.2%). The increased ecto-5' -nucleotidase activity due to the IP procedure decreased according to the order of IP1 to IP4 groups. Infarct size was inversely correlated with ecto-5'-nucleotidase activity (P < 0.001). An inhibitor of ecto-5'-nucleotidase blunted the infarct size-limiting effect of IP. The infarct size-limiting effect of IP decreased as the activation of ecto-5'-nucleotidase was blunted. These results suggest that ecto-5'-nucleotidase activity plays a key role in the cardioprotection of IP.

10] Nitric oxide- and nitric oxide donor-induced relaxation

Publisher Summary This chapter discusses some of the unique characteristics of nitric oxide (NO)- and NO donor-induced coronary vasorelaxation. Similar responses can be extrapolated to other blood vessels and different animal species, including humans. The NO donors discussed in the chapter include an example of the nitrosothiol derivatives, S-nitroso-N-acetylpenicillamine (SNAP), and an example of the nitrovasodilators, sodium nitroprusside. The chapter discussed the vasorelaxant effects of peroxynitrite, an intermediate metabolic degradation product of NO and superoxide anion that is capable of producing a nitrosothiol derivative and/or direct interaction with vascular smooth muscle cells in the activation of guanylate cyclase and production of cyclic guanosine monophosphate (GMP). The vasorelaxation effect of NO and NO donors on coronary arteries is discussed because of their importance in various cardiovascular syndromes, and because of the familiarity with this blood vessel system, particularly with the epicardial conduit arteries of adult dogs. The extent of NO- and NO donor-induced vasorelaxation effects is enhanced with low oxygen tension and superoxide dismutase and inhibited by hemoglobin. The exact role of these NO and NO donors in the treatment of various clinical and pathophysiological conditions requires further study.

血栓形成よりみたHot-tip法を用いたレーザー血管形成術における至適条件

We evaluated thrombogenesis in laser thermal angioplasty in experimental model.Study I): Metal tip probe was introduced through the carotid artery and,laser ablation was performed on the inner surface of the femoral artery of the adult mongrel dogs. Laser ablation was carried out with the energy of 16J, 20J, 24J, 30J which is same energy of clinically used to the infrainguinal regions. After laser ablation, intimal surface was observed with angioscope. Plasma levels of the thromboxane B2 and 6-keto-PGFI α were measured. Study II): Laser ablation was performed to the bilateral femoral arteries with the energy of 16J, 20J, 24J, 30J, 45J. After laser ablation,IndiumIII labeled-platelet (I*P) was infused and, after 3 hours,I*P deposition was measured in each segment and normalized to 1 mm2 intimal surface. Results; Study I) Large thrombus was not observed angioscopically in each cases.Only in the cases which plasma level of thromboxane B2 was increased above three times as before laser ablation, micro thrombus was observed. Study II) Platelet density was significantly higher in 45J cases than the other cases,in 30J cases higher than control. There were no differences between 16, 20, 24J cases and control.These results suggested that laser energy which we use clinically is in the safe range from the view point of thrombogenesis.

Flow-Pressure Drop Measurement and Calculation in a Tapered Femoral Artery of a Dog

Flow-Pressure Drop Measurement and Calculation in a Tapered Femoral Artery of a Dog

Phenotypic reversion of smooth muscle cells in hybrid vascular prostheses

Our purpose was to evaluate whether or not and when phenotypic modulation of smooth muscle cells (SMCs) in hybrid vascular prostheses preincorporated with SMCs occurs upon implantation. Two types of hybrid vascular grafts incorporated with vascular cells derived from canine jugular veins were prepared: grafts containing a collagen gel layer covered with an endothelial monolayer at the luminal surface (Model I graft) and those containing an endothelial monolayer and SMC multilayer (Model II graft). They were bilaterally implanted into carotid arteries of the same dogs from which the cells had been harvested for 2 wk ( n = 3) and 12 wk ( n = 3). The time-dependent changes in populations of three SMC phenotypes (synthetic, intermediate, and contractile) in the neoarterial layers were quantified by morphometric evaluation using a transmission electron microscope in hybrid vascular grafts. Before implantation, all the SMCs were of the synthetic phenotype. In Model II grafts at 2 wk, synthetic and intermediate SMCs were dominant especially in the luminal layer. On the other hand, neoarterial layers at 12 wk were dominated by contractile SMCs, which were evenly distributed throughout the entire neoarterial tissues. A markedly delayed phenotypic reversion was noted for the Model I grafts at 12 wk. In the hybrid grafts, during about 3 mo of implantation, neoarterial SMCs transformed from the synthetic to the contractile phenotypes, which was promoted by SMC incorporation.

Endothelium-dependent hyperpolarization. Beyond nitric oxide and cyclic GMP.

Blood flow and blood pressure are determined by an integration of reflex, humoral, and local vascular control mechanisms. Knowledge of these mechanisms has mushroomed over the past 15 years, particularly in the area of local endothelium-dependent vasomotor control. This has stemmed from the pioneering report in 1980 by Robert Furchgott1 demonstrating that the endothelium releases a vasodilator substance in response to acetylcholine. This concept has been expanded with knowledge that the endothelium releases a variety of relaxing and contracting factors that regulate the underlying smooth muscle.2 The most widely known endothelium-derived relaxing factor, nitric oxide, is released from endothelial cells in response to shear stress or stimulation of different receptors for a variety of neurohumoral mediators on the endothelial cell surface.3 The increase in endothelial cell calcium initiated by these stimuli increases the activity of a constitutively expressed enzyme, nitric oxide synthase, which converts l-arginine to nitric oxide and citrulline.4 5 6 7 Nitric oxide thus formed diffuses to and inhibits contraction of the underlying vascular smooth muscle.3 The physiological significance of the production of endothelial nitric oxide is suggested by the vasoconstriction observed in most vascular beds8 9 10 11 12 13 and the increase in systemic arterial blood pressure,14 15 16 which occurs on infusion of inhibitors of nitric oxide synthase. This observation further implies that under normal conditions, endothelial cells are locally liberating nitric oxide which effectively inhibits vasoconstriction arising by other mechanisms. Thus, normal vascular homeostasis depends in the periphery on a balance between neurally and humorally mediated vasoconstriction in skeletal muscle, mesentery, and the kidney, and local endothelium-dependent vasodilatation. In the truly vital areas of the heart, brain, and genitalia, vasodilator neural mechanisms reinforce the vasodilator influence of the endothelium.17 All is not known regarding the …

Eicosapentanoic Acid Reduces the Intimal Thickening of Autogenous Vein Grafts and Enhances Endothelium-Derived Relaxing Factor

The present study examined the effect of purified eicosapentanoic acid (EPA) on intimal thickening of an autogenous vein graft. In addition, experiments were performed to determine whether EPA supplementation would alter the endothelium-dependent responses of the reversed vein graft. Segments of femoral veins were grafted into the femoral arteries of dogs. Six dogs received regular chow (control group) and six other dogs regular chow with 1500 mg/day 90.0% pure EPA (EPA group). At 6 weeks after surgery, the vein grafts were removed from the dogs, cut into rings, and suspended in organ chambers for isometric tension recording. In some rings, the endothelial cells were removed. When the rings taken from the control group were contracted with norepinephrine, adenosine diphosphate (ADP) and A23187 caused endothelium-dependent relaxations. In the EPA group, the endothelium-dependent responses to ADP were significantly augmented, while A23187 caused comparable endothelium-dependent relaxations. Direct relaxation in response to sodium nitroprusside was comparable between the two groups. Intimal thickening of the grafts in the control group (29.0 ± 1.8 μm) was significantly ( P < 0.05) greater than in the EPA group (12.5 ± 1.8 μm). These results suggest that EPA enhances the release of endothelium-derived relaxing factor in autogenous vein grafts. This may be one of the effects of EPA in reducing the intimal thickening of autogenous vein grafts.

Endothelial modulation of beta-adrenergic dilation of large coronary arteries in conscious dogs.

Endothelium-derived relaxing factors have been described as important intermediates in beta-adrenergic vasodilation of resistance coronary vessels, but their involvement at the level of large epicardial coronary arteries remains controversial. Therefore, we examined the role of vascular endothelium in the beta-adrenergic-mediated vasodilation of large epicardial coronary arteries in conscious dogs. Nine dogs were instrumented for measurement of left circumflex coronary artery diameter (CD) by sonomicrometry and coronary blood flow velocity (CBFv) with a Doppler technique in response to graded doses of isoproterenol (0.001 to 0.1 microgram/kg IV bolus). Under control conditions, isoproterenol induced dose-dependent increases in CD and CBFv. When CBFv was kept constant at its baseline value by inflation of a cuff occluder, isoproterenol still induced dose-dependent increases in CD, but the latter were of lesser magnitude than those observed under normal CBFv conditions (110 +/- 20 versus 170 +/- 30 microns, respectively, ie, a reduction of 33% of the dilatory response at 0.1 microgram/kg, P < .01). In the same dogs, the coronary endothelium was then mechanically removed at the site of CD measurement by a balloon angioplasty technique. After this procedure, the dose-dependent increases in CD induced by isoproterenol under either normal or controlled CBFv conditions were overimposable, and their magnitude was similar to that of the increases observed in the presence of an intact endothelium when CBFv was kept constant. After beta 1-adrenergic receptor blockade by atenolol (1 mg/kg), isoproterenol-induced increases in CD were abolished either when CBFv was kept constant or after endothelium removal. In conscious dogs, the direct stimulating effect of isoproterenol on beta 1-adrenergic receptors is endothelium-independent at the level of large coronary arteries. The endothelium reinforces the dilatory response to isoproterenol through an indirect, flow-dependent mechanism.

Heterogeneity of neurogenic responses in intra- and extrameningeal arteries of dogs.

1. Neurogenic responses to transmural electrical stimulation were examined in endothelium-denuded extrameningeal (vertebral and carotid) and intrameningeal (spinal, basilar and middle cerebral) arteries isolated from dogs. 2. In the extrameningeal arteries, transmural electrical stimulation produced a phasic contraction. This contraction was abolished by tetrodotoxin, prazosin and guanethidine. However, alpha,beta-methylene ATP and NG-nitro-L-arginine (L-NOARG) had no significant effect on the contractile responses. 3. In the intrameningeal arteries, the neurogenic responses to electrical stimulation were composed of a transient contraction and relaxation. The transient contraction was selectively inhibited by guanethidine L-NOARG abolished the relaxation but not the contraction induced by electrical stimulation. Prazosin had no effect on either neurogenic response. 4. Noradrenaline produced a large contraction in the extrameningeal arteries which was selectively inhibited by prazosin. alpha,beta-Methylene ATP produced neither contraction nor inhibition of the response to noradrenaline in the extrameningeal arteries. 5. In the intrameningeal arteries, alpha,beta-methylene ATP produced a greater contraction than noradrenaline. The response to alpha,beta-methylene ATP was selectively abolished by desensitization of P2x-purinoceptors with alpha,beta-methylene ATP itself. The contractile response to noradrenaline was inhibited by rauwolscine but not by prazosin. 6. ATP produced endothelium-dependent relaxations in the extrameningeal and intrameningeal arteries, which were attenuated by endothelium removal. 7. NADPH diaphorase-positive fibres were dense in the middle cerebral and basilar arteries but rare or absent in the spinal artery. In the extrameningeal arteries diaphorase-positive traces were observed in the vasa vasorum. 8. The present findings indicate that the neurogenic responses of intrameningeal arteries of dogs are composed of NO-ergic and sympathetic purinergic components, while the extrameningeal arteries tested produced only sympathetic adrenergic responses, suggesting that regional heterogeneity may be associated with a sudden transition in innervation and receptor expression at the meninx.

Phenotypic reversion of smooth muscle cells in hybrid vascular prostheses.

Our purpose was to evaluate whether or not and when phenotypic modulation of smooth muscle cells (SMCs) in hybrid vascular prostheses preincorporated with SMCs occurs upon implantation. Two types of hybrid vascular grafts incorporated with vascular cells derived from canine jugular veins were prepared: grafts containing a collagen gel layer covered with an endothelial monolayer at the luminal surface (Model I graft) and those containing an endothelial monolayer and SMC multilayer (Model II graft). They were bilaterally implanted into carotid arteries of the same dogs from which the cells had been harvested for 2 wk (n = 3) and 12 wk (n = 3). The time-dependent changes in populations of three SMC phenotypes (synthetic, intermediate, and contractile) in the neoarterial layers were quantified by morphometric evaluation using a transmission electron microscope in hybrid vascular grafts. Before implantation, all the SMCs were of the synthetic phenotype. In Model II grafts at 2 wk, synthetic and intermediate SMCs were dominant especially in the luminal layer. On the other hand, neoarterial layers at 12 wk were dominated by contractile SMCs, which were evenly distributed throughout the entire neoarterial tissues. A markedly delayed phenotypic reversion was noted for the Model I grafts at 12 wk. In the hybrid grafts, during about 3 mo of implantation, neoarterial SMCs transformed from the synthetic to the contractile phenotypes, which was promoted by SMC incorporation.

Intrarenal infusions of endothelin in conscious dogs: interactions with prostanoids and angiotensin II.

Endothelin (2, 5, and 10 pmol/kg/min) was infused into the renal artery of conscious dogs, producing graded and progressive reductions in renal blood flow (RBF) without initial vasodilatation, parallel reductions in glomerular filtration rate (GFR), and reduced Na+ excretion, but little change in urine flow. Pretreatment of the dogs with either ibuprofen (20 mg/kg orally) or aspirin (30 mg/kg p.o.) did not significantly alter the effects of endothelin (5 pmol/kg/min) on RBF, GFR, or Na+ excretion. However, endothelin caused antidiuresis in these cyclooxygenase-inhibited dogs, indicating that the effects of endothelin on water reabsorption were prostanoid mediated. Treatment with captopril (1.5 mg/kg + 0.5 mg/kg/h) did not significantly alter any of the responses to endothelin. The local effects of endothelin in the kidneys of conscious dogs were vasoconstriction and reduced Na+ excretion which were not mediated or modified by either angiotensin II or prostanoids.