摘要:

The purpose of this study was to evaluate the cardioprotective effects of carvedilol, a β-adrenergic blocker and vasodilator, in two models of ischemic myocardial damage in the rat. Following coronary artery occlusion for 0.5 h and reperfusion for 24 h (MI/R group), left ventricular (LV) injury was determined by planimetric analysis of triphenyltetrazolium chloride-stained tissue, and polymorphonuclear leukocyte infiltration was assessed by measuring myeloperoxidase (MPO) activity. In the vehicle-treated MI/R group, infarct size was 14.2 ± 1.3% of the LV (n = 16), and MPO activity was increased to 2.8 ± 0.7 from 0.14 ± 0.03 U/g tissue in the vehicle-treated sham-occluded group (p < 0.01). Carvedilol (1 mg/kg i.v., 15 min prior to coronary artery occlusion and at 3.5 h following reperfusion) reduced myocardial infarct size to 7.5 ± 1.2% of the LV (n = 14; p < 0.01) and attenuated the increase in MPO activity to 1.4 ± 0.4 U/g tissue (p < 0.05). A lower dose of carvedilol (i.e. 0.3 mg/kg i.v.) did not limit myocardial infarct size or the increase in MPO activity. In a model of permanent coronary artery occlusion, 24-hour survival was reduced from 85% in sham-occluded animals (n = 38) to 44% in the vehicle-treated MI group (n = 84; p < 0.01). In comparison to the vehicle-treated MI group, carvedilol (0.3 mg/kg i.v., 15 min prior to coronary artery occlusion and 1 mg/kg 4 h after occlusion) improved survival by 55% (n = 64; p < 0.05, compared to the vehicle-treated MI group), whereas the same dose of propranolol (n = 42) had no significant effect on survival. These results indicate that carvedilol reduces myocardial ischemia/reperfusion injury, and significantly improves survival in a permanent coronary artery occlusion model of myocardial infar

ISSN:0031-7012    

DOI:10.1159/000138934

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

An increase in pulmonary vascular resistance (PVR) after cyclooxygenase inhibition (COI) is well documented in the dog, but the site of vasoconstriction to chemically distinct cyclooxygenase inhibitors is largely unknown. The purpose of the present study was to examine and compare equimolar concentrations of three chemically unrelated cyclooxygenase inhibitors, indometacin (INDO; n = 6), meclofenamate (MECLO; n = 6) and ibuprofen (IBU; n = 5), upon the longitudinal distribution of PVR in the isolated canine lower left lung lobe perfused at constant flow with autologous blood. At successive increases in the blood concentration of each cyclooxygenase inhibitor, PVR was partitioned into upstream (arterial, Ra), middle (Rm) and downstream (venous, Rv) resistance by arterial and venous flow occlusion with capillary pressure estimated by a double flow occlusion technique. All three cyclooxygenase inhibitors produced significant pulmonary vasoconstriction with the largest increase in PVR after INDO (104 ± 21 %) and the smallest after IBU (69 ± 10%). The PVR increase in the INDO and MECLO group was related to an elevation in both Ra (p < 0.01) and Rv (p < 0.01), whereas only Rv was increased by IBU (p 0.05), capillary pressure was increased from pretreatment levels by each cyclooxygenase inhibitor. Although each of the three chemically distinct cyclooxygenase inhibitors raised PVR, the segmental distribution of PVR and the magnitude of the capillary pressure increase varied at equimolar blood concentratio

ISSN:0031-7012    

DOI:10.1159/000138935

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The administration of the antithyroid drug methimazole to rats via drinking water prevented the development of hypertension that usually accompanies subtotal nephrectomy and saline drinking (1% NaCl). In methimazole-treated rats, elevated blood pressure induced 5 weeks previously returned to normotensive levels. Pressor responsiveness to angiotensin, vasopressin and norepinephrine in unanesthetized rats was studied after prevention of hypertension in control, low-renal-mass hypertensive (LRM) and low-renal-mass methimazole-treated (LRM-M) rats, and in the reversion study in LRM and LRM-M rats. In LRM rats, responsiveness to vasoconstrictors was increased, whereas responsiveness to vasoconstriction was clearly reduced in LRM-M rats after prevention and reversion studies. These results suggest that (a) thyroid hormones are required in the early and established phases of LRM hypertension, and (b) the decreased pressor responsiveness to vasoconstrictors may play a role in the prevention and reversion of this type of hypertension following methimazole administration. However, the changes in pressor responsiveness may also be secondary to the reduction in blood pressure.

ISSN:0031-7012    

DOI:10.1159/000138936

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We have investigated the presence and nature of muscarinic binding sites on membranes from cultured bovine pulmonary arterial endothelial cells (BPAE). BPAE were harvested and subcultured nonenzymatically; experiments were performed 3-5 days postconfluence and between 10 and 25 passage numbers. Utilizing radioligand binding techniques with the muscarinic receptor antagonists [3H]3-quinuclidinyl benzilate ([3H]QNB) and [3H]N-methylscopolamine ([3H]MS) as probes, we identified a small population of atropine-sensitive muscarinic sites (1,800-2,000 sites/cell or 7-8 fmol/mg protein). Muscarinic binding sites on BPAE membranes resembled classical muscarinic receptors in that (a) the binding of 2 nM [3H]QNB was inhibited by muscarinic agonists and antagonists, (b) [3H]QNB binding was 30 times more sensitive to R(–)- than to S(+)-QNB, (c) binding of the muscarinic receptor agonist carbamylcholine involved high and low affinity components, (d) the stable GTP analog, Gpp(NH)p (100 µM) shifted agonist binding curves to the right by a factor of three, and (e) the high affinity binding of the agonist [3H]oxotremorine-M to muscarinic receptors was depressed by Gpp(NH)p. On the other hand, gallamine, which allosterically regulates muscarinic receptor binding in other tissues, did not affect the rates of dissociation of [3H]QNB, [3H]MS or [3H]oxotremorine-M from BPAE binding sites. We concluded that BPAE in culture exhibit muscarinic binding sites which possess many but not all of the properties associated with classical muscarinic recepto

ISSN:0031-7012    

DOI:10.1159/000138937

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We studied the effect of inhibition of oxyradical formation and of endogenous glutathione (GSH) depletion on lesion formation in the gastrointestinal tract in a modified rat hemorrhagic shock model (1 h hypotension and 1 h reperfusion). Allopurinol, an inhibitor of xanthine oxidase, did not protect against lesion formation. This suggests that oxygen radicals generated from xanthine oxidase may not be the major cause of injury under these conditions of prolonged ‘ischemia’-reperfusion. Phorone (diisopropylideneacetone), a GSH depletor, decreased mucosal GSH levels in the corpus, duodenum and small intestine, and also significantly reduced lesion formation histologically in the corpus, antrum, duodenum and small intestine. However, there was no significant differences in mucosal blood flow (as estimated by changes in mucosal hemoglobin concentrations and oxygen saturation of mucosal hemoglobin) in the corpus, antrum, duodenum and small intestine between phorone-pretreated and control rats. We conclude that phorone decreased mucosal GSH concentrations and exerted a protective effect against hemorrhagic shock-induced gastrointestinal mucosal lesions. The protective effect appears to be independent of mucosal blood f

ISSN:0031-7012    

DOI:10.1159/000138938

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We determined a protective action of probucol (4,4’-[isopropylidenedithio]bis[2,6-di-tert-butylphenol]) on the reduction of serum immunoreactive insulin (IRI) levels by recombinant human interleukin-1β (IL-1) in adrenalectomized rats. IL-1 reduced the serum IRI levels 4 h after injection in rats fed a standard diet. However, IL-1 failed to inhibit serum IRI levels in rats fed a diet containing 1% probucol. In contrast, IL-1 decreased plasma glucose levels in both groups. Although IL-1 reduced plasma prostaglandin (PG) E2 levels in standard diet-fed rats, IL-1 did not affect plasma PGE2 levels in the animals fed the probucol-containing diet. The present study suggested that the free radical scavenger action of probucol can block the IL-1 effect on serum IRI leve

ISSN:0031-7012    

DOI:10.1159/000138939

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138940

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138941

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138933

出版商:S. Karger AG    

年代:1992

数据来源: Karger