Medial Smooth Muscle Cell Proliferation in the Balloon Injured Rabbit Aorta: Effect of a Thiazole Compound with Platelet Inhibitory Activity

1984 ◽  
Vol 51 (01) ◽  
pp. 075-078 ◽  
Author(s):  
R G Schaub ◽  
C A Simmons
Keyword(s):  
Smooth Muscle ◽  
Platelet Aggregation ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Surface Characteristics ◽  
Inhibitory Effect ◽  
Lesion Size ◽  
Blue Staining ◽  
Morphologic Characteristics ◽  
Time Period

SummaryTwenty-seven adult male New Zealand rabbits (3–4 kgs) were used in this study. Six rabbits received vehicle, 3 groups of 6 each received doses of 4,5-bis(p-methoxyphenyl)-2-(trifluoromethyl)- thiazole, (U-53,059), at 0.3 mg/kg, 3.0 mg/kg and 30.0 mg/kg/day respectively. Drug and vehicle doses were given orally each day starting 3 days before balloon injury and continuing for the entire 2 week time period. Three rabbits were used as nontreated sham controls. In the vehicle and U-53,059 treated groups aortae were denuded of endothelial cells by balloon catheter injury. Two weeks after injury platelet aggregation to collagen was measured and the aortae removed for analysis of surface characteristics by scanning electron microscopy and lesion size by morphometry. All doses of U-53,059 inhibited platelet aggregation. The 3.0 and 30.0 mg/kg groups had the greatest inhibitory effect. All balloon injured aortae had the same morphologic characteristics. All vessels had similar extent and intensity of Evan’s blue staining, similar areas of leukocyte/platelet adhesion, and a myointimal cell cover of transformed smooth muscle cells. The myointimal proliferative response was not inhibited at any of the drug doses studied.

Quantitation of Platelet Adherence to Rabbit Aortae and Platelet Survival After two Injuries with a Balloon Catheter

1979 ◽  
Author(s):  
R.L. Kinlough-Rathbone ◽  
H.M. Groves ◽  
S. Maric ◽  
M.A. Packham ◽  
J.F. Mustard
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Platelet Adherence ◽  
Platelet Survival ◽  
Single Balloon

Following a single balloon catheter injury to a rabbit aorta (INJ 1) a monolayer of platelets covers the subendothelium within 10 min, the surface becomes relatively non-reactive to further platelet accumulation and platelet survival is not altered. We have now studied whether a second similar injury (INJ 2) of the non-reactive, smooth muscle cell-rich neointima 7 days after INJ 1 makes the surface of the neointima reactive to platelets or alters platelet survival. 51Cr-platelet adherence to the neointima of aortae subjected to INJ 2 in vitro 7 days after an initial in vivo injury was not significantly different from the adherence following a single in vitro injury (16,600 ± 3100 platelets/mm2 and 27,600 ± 4000 respectively, ρ > 0.2). In vivo adherence of 51Cr-platelets to the surface of rabbit aortae was similar following INJ 1 (0.084 ± 0.009% of the circulate, platelets) and INJ 2 (0.130 ± 0.03%, p > 0.2). Platelet survival after injury to the neointima was not significantly different in animals with an undamaged aortic endothelium (74.6 ± 5.9 hr and 80.2 ± 4.3 hr respectively, ρ > 0.5). Thus, a second injury involving the smooth’ muscle cell-rich neointima that forms after removal of the endothelium with a balloon catheter does not cause more platelets to accumulate than the initial injury, nor shorten platelet survival.

Inhibitory effect of clentiazem (TA-3090), a new calcium antagonist, on balloon catheter-induced intimal thickening of rabbit aorta

1993 ◽  
Vol 7 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Yoshihisa Saso ◽  
Akio Ohtani ◽  
Akio Odawara ◽  
Hitoshi Iwasaki ◽  
Kohki Takashima ◽  
...  
Keyword(s):  
Calcium Antagonist ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Intimal Thickening

The Inhibitory Effect of GR32191, a Thromboxane Receptor Blocking Drug, on Human Platelet Aggregation, Adhesion and Secretion

1989 ◽  
Vol 61 (03) ◽  
pp. 429-436 ◽  
Author(s):  
E J Hornby ◽  
M R Foster ◽  
P J McCabe ◽  
L E Stratton
Keyword(s):  
Platelet Aggregation ◽  
Thrombus Formation ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Camp Phosphodiesterase ◽  
Platelet Protein ◽  
Thromboxane Receptor ◽  
Serotonin Secretion

SummaryGR32191, a potent selective thromboxane receptor antagonist, has been shown to inhibit completely prostaglandin endoperoxide and thromboxane A2 (TxA2)-induced platelet aggregation, [14C]-serotonin secretion and β-thromboglobulin secretion. Deposition of human platelets onto damaged rabbit aorta in vitro is reduced in the presence of GR32191 which appears to inhibit aggregation of platelets but not direct adhesion of platelets to subendothelium. The effects of non-prostanoid platelet activating agents whose mode of action requires the biosynthesis of TxA2 are also inhibited by GR32191. Prostanoids which inhibit platelet function, such as prostacyclin or PGD2, retain their inhibitory properties in the presence of GR32191 which does not inhibit phospholipase A2, prostaglandin cyclooxygenase, thromboxane synthase, 12-lipoxygenase or cAMP phosphodiesterase activity. The inhibitory action of GR32191 on platelet aggregation, mural thrombus formation and platelet protein storage granule secretion suggests that it has potential in treatingthrombotic disease in man.

Quantitation of Platelet Adherence to Rabbit Aortae and Platelet Survival After Two Injuries With a Balloon Catheter

1979 ◽  
Author(s):  
R Kinlough-Rathbone ◽  
H Groves ◽  
S Maric ◽  
M Packham ◽  
J Mustard
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Platelet Adherence ◽  
Platelet Survival ◽  
Single Balloon

Following a single balloon catheter injury to a rabbit aorta (INJ 1) a monolayer of platelets covers the subendothelium within 10 min, the surface becomes relatively nonreactive to further platelet accumulation and platelet survival is not altered. We have now studied whether a second similar injury (INJ 2) of the non-reactive, smooth muscle cell-rich neointima 7 days after INJ 1 makes the surface of the neointima reactive to platelets or alters platelet survival. 51Cr-platelet adherence to the neointima of aortae subjected to INJ 2 in vitro 7 days after an initial in vivo injury was not significantly different from the adherence following a single in vitro injury (16,600 ± 3100 platelets/mm2 and 27,600 ± 4000 respectively, p > 0.2). In vivo adherence of 51Cr-platelets to the surface of rabbit aortae was similar following INJ 1 (0.084 ± 0.009% of the circulating platelets) and INJ 2 (0.130 ± 0.03%, p > 0.2). Platelet survival after injury to the neointima was not significantly different in animals with an undamaged aortic endothelium (74.6 ±5.9 hr and 80.2 ± 4.3 hr respectively, p > 0.5). Thus, a second injury involving the smooth muscle cell-rich neointima that forms after removal of the endothelium with a balloon catheter does not cause more platelets to accumulate than the initial injury, nor shorten platelet survival.

The Inhibitory Effect Of Dilazep On Adhesion And Aggregation Of Platelet Following Aortic Intimal Injury In Rabbit

1981 ◽  
Author(s):  
A Sumiyoshi ◽  
T Hayashi ◽  
M Fujii
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Endothelial Injury ◽  
Platelet Adhesion And Aggregation ◽  
Injured Area ◽  
Polyethylene Tubing

The inhibitory effect of dilazep and aspirin on in vivo platelet adhesion and aggregation in rabbit aorta subjected to endothelial injury was investigated. Endothelial injury was induced by insertion of polyethylene tubing from the femoral artery into the aorta. In the beginning before surgery, experimental animals were intravenously given sufficient drug to inhibit platelet aggregation in vitro in response to ADP and collagen. For a quantitative analysis of platelet accumulation on the damaged aortas, 51Cr-labeled platelets were used. For morphological study, the aortas were fixed by perfusion at one hour after injury and examined by light and scanning electron microscopy for platelet adhesion and aggregation in injured area.Radioactivity of damaged aortas in rabbits administered dilazep (50 or 100 μg/kg) or aspirin (10 mg/kg) was significantly lower than in rabbits untreated by drug. Dilazep and aspirin did not prevent completely the adherence of platelets on injured area of the aorta, but inhibited considerably the platelet aggregation to form raised platelet thrombus.

Synthetic atrial peptide inhibits intracellular calcium release in smooth muscle

1986 ◽  
Vol 250 (1) ◽  
pp. C171-C174 ◽  
Author(s):  
K. D. Meisheri ◽  
C. J. Taylor ◽  
H. Saneii
Keyword(s):  
Smooth Muscle ◽  
Calcium Release ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Physiological Salt Solution ◽  
Phasic Contraction ◽  
Dependent Inhibition ◽  
Isolated Rabbit Aorta ◽  
Dose Dependent Inhibition ◽  
45Ca Efflux

The effects of a synthetic atrial peptide (atriopeptin II; AP II) on the agonist-induced intracellular Ca2+ release was examined in the isolated rabbit aorta. The agonist-induced phasic contraction in a Ca2+-free physiological salt solution containing 2 mM ethyleneglycol-bis(beta-aminoethyl-ether)-N,N'-tetraacetic acid (EGTA-PSS) was used as an indicator of the intracellular Ca2+ release. The addition of AP II (10(-9)-10(-7) M) for 15 min to the tissue during the EGTA-PSS exposure caused a dose-dependent inhibition of norepinephrine (NE; 10(-6) M)-induced phasic contraction. The half-maximal inhibiting concentration of AP II was 3 X 10(-9) M, with 10(-7) M AP II causing 91% inhibition. This was confirmed by studying the inhibitory effect of AP II (10(-7) M) on NE-stimulated 45Ca efflux. Furthermore, the internal Ca2+ release by histamine (10(-5) M) and caffeine (25 mM), both of which share this internal Ca2+ pool with NE, was also inhibited by AP II. Thus AP II appears to be a potent inhibitor of the intracellular Ca2+ release that is utilized by various agonists for the activation of vascular smooth muscle. This may be an important mechanism by which AP II produces relaxation of blood vessels.

Inhibition of Intimal Proliferation of Rabbit Aorta by Ticlopidine

1979 ◽  
Author(s):  
A. H. Reece ◽  
P.L. Walton
Keyword(s):  
Smooth Muscle ◽  
Cell Injury ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Endothelial Cell Injury ◽  
Intimal Proliferation ◽  
Image Analyser ◽  
Effect Of Treatment ◽  
C 30 ◽  
C 50

Proliferation of smooth muscle cells in the intima of arteries at sites adjacent to damaged endothelium may be stimulated by growth factors released from platelets. We have studied the effect of treatment with two inhibitors of platelet function, Ticlopidine and Sulphlnpyrazone, on the rate and extent of intimal proliferation In rabbit abdominal aorta following endarterectomy using a balloon catheter. Aortas were removed at Intervals after surgery, fixed, sectioned and the extent of intimal proliferation was measured using an Image analyser (Quantlmet 720). The arc a of Intimal growth as a percentage of total area of aorta was 42.4±2.8,22.3±1.2 and 50.9±2.0, 33.9±2.0 in control and Ticlopidine treated animals 30 and 60 days after endarterectomy, respectively. Thus treatment with Ticlopidine (50mg/kg/day P. O.) produced a highly significant (p<.001) reduction In the extent of intimai growth In these animals (c 50%), where as Sulphlnpyrazone (50mg/kg/day P. O.) had no effect. ADP Induced platelet aggregation was reduced (c 30%) during the treatment with Ticlopidine but not during treatment with Sulphlnpyrazone.These findings indicate that Ticlopidine treatment limits intimai proliferation In rabbits following endothelial cell Injury and may be of value in limiting this process In man.

Endotoxin Inhibits Prostacyclin Release From Rabbit Aorta

1981 ◽  
Author(s):  
J Zahavi ◽  
A C Honey ◽  
J Westwick ◽  
V V Kakkar
Keyword(s):  
Platelet Aggregation ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
White Female ◽  
Time Intervals ◽  
E Coli ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Mean ◽  
Dose Dependent

Released prostacyclin (PGI2) activity has been studied in aortic rings of 19 New Zealand white female rabbits. These rings produced a potent inhibitor of platelet aggregation, identified as PGI2. All the rabbits were anaesthetized with pentobarbital and thereafter a solution of endotoxin (E. Coli, 0111, B4, Difco Lab.) was injected intravenously to 7 rabbits (304μg/kg every 15 min during 1 hour to achieve an estimated plasma level of 1-2 μg/ml). Another 5 rabbits served as controls and were injected with saline. After 1 hour the aorta was rapidly excised, cleaned, cut into small rings and the released PGI2 activity studied at various time intervals (5-30 min) at 37°C. The mean release of PGI2 (in pg/mg wet tissue) in the control rabbits was 201 (range 50-443). It decreased significantly to 104 (range 0-237) after 30 min. In the endotoxaemic rabbits, the initial PGI2 release was only 73 (range 0-329) (p<0,008 compared to control rabbits). This level did not change with time and was 71.9 (range 0-261) after 30 min suggesting that the “endotoxinemic” vessels were initially relatively exhausted and were not able to release PGI2. In the remaining 7 rabbits the aorta was removed immediately after anaesthesia and aortic rings incubated for 5-30 min Krebs-Henleit buffer or endotoxin 0.2-10 μg/ml and the released PGI2 activity studied. There was a dose dependent inhibition which was more pronounced after 30 min incubation.The decrease in PGI2 release from rabbit aorta following endotoxaemia removes the inhibitory effect on platelet aggregation of the arterial vessel wall and consequently may contribute to the development of a thrombogenic state.

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