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L Lin

Publications and source records attributed to L Lin.

At least 379 records · Page 21Linked to original sources
PubMed1992

Pressor and renal vasoconstrictor effects of NG-nitro-L-arginine as affected by blockade of pressor mechanisms mediated by the sympathetic nervous system, angiotensin, prostanoids and vasopressin.

Inhibitors of nitric oxide (NO) synthesis increase blood pressure and decrease regional blood flow. We investigated whether blockade of the renin-angiotensin, sympathetic nervous, prostaglandin or vasopressin systems attenuates the effects of the NO synthesis inhibitor NG-nitro-L-arginine (L-NOARG) on mean arterial pressure and renal blood flow in anesthetized male Sprague-Dawley rats. Treatment with L-NOARG (10 mg kg-1, i.v. bolus plus infusion at 20 mg kg-1 hr-1) increased mean arterial pressure from 113 +/- 2 to 133 +/- 4 mm Hg, decreased renal blood flow from 7.7 +/- 0.6 to 4.3 +/- 0.6 ml min-1 g-1 and increased renal vascular resistance from 15.8 +/- 1.8 to 36.9 +/- 6.1 mm Hg/ml min-1 g-1. These effects were attenuated in rats pretreated with L-arginine to interfere with the inhibitory action of L-NOARG on NO synthesis, but not in rats pretreated with D-arginine. Acetylcholine did not relax aortic rings taken from rats treated with L-NOARG, consistent with inhibition of NO-mediated vasorelaxation. The pressor and renal vasoconstrictor effects of L-NOARG were not impaired in rats separately pretreated with either chlorisondamine, captopril, prazosin, indomethacin or d(CH2)5Tyr(Me)AVP, or in rats pretreated with chlorisondamine, captopril and indomethacin in combination. Collectively, these data argue against significant contribution of the sympathetic nervous system, the renin-angiotensin system, vasopressor prostanoids or vasopressin to the mechanisms of L-NOARG-induced elevation of mean arterial pressure and renal vasoconstriction in anesthetized rats.

Angiotensin II↗
PubMed1992

Photochemical inactivation of viruses and bacteriophage in plasma and plasma fractions.

Transfusion-associated transmission of viral diseases remains a problem. A number of methods have been developed to inactivate viral pathogens in plasma and plasma fractions, including: dry heating, wet heating, solvent-detergent treatment, and immunoaffinity purification. While some of these methods successfully inactivate pathogenic viruses, inactivation may be incomplete or result in damage to labile plasma proteins. We have developed a method of photochemical decontamination (PCD) using psoralens and long wavelength ultraviolet light to inactivate pathogenic viruses. In the present study, a spectrum of model viruses have been added to plasma and plasma fractions to examine the efficiency of photochemical decontamination and the effects on labile plasma coagulation factors. Both RNA and DNA viruses have been inactivated under conditions which permit preservation of coagulation protein function. PCD technology appears to offer a promising solution to decontamination of blood products.

Bacteriophages↗
PubMed1991

Peripheral-type benzodiazepines inhibit proliferation of astrocytes in culture.

Peripheral-type benzodiazepine (BZD) receptors have been identified in brain and are predominantly localized to astrocytes. To determine their potential role in controlling astroglial proliferation, DNA synthesis, growth curves and mitotic index were investigated in primary astrocyte cultures which had been exposed to Ro5-4864 (a peripheral-type BZD ligand) and PK11195 (a peripheral-type BZD receptor antagonist). There was a dose-dependent inhibition of mitosis when two-week-old cells in culture were exposed to 50 nM, 500 nM, 1 microM and 10 microM Ro5-4864 for 24 h. Exposure of 5-, 8-, 12- and 15-day-old cultures to Ro5-4864 and PK11195 for 24 h did not affect growth rate and DNA synthesis; however, continuous exposure to 10 microM Ro5-4864 caused a persistent inhibition of cell growth and [3H]thymidine incorporation (P less than 0.05) while nanomolar concentrations did not cause any significant change. Concurrent administration of Ro5-4864 with PK11195 resulted in a partial reversal of Ro5-4864-induced inhibition in DNA synthesis and mitosis. These results indicate that peripheral-type BZDs are capable of inhibiting proliferation of astrocytes in culture.

Animals↗
PubMed1991

Antiproliferative effects of oxygenated sterols: positive correlation with binding affinities for the antiestrogen-binding sites.

Oxygenated derivatives of cholesterol have long been known to exhibit antiproliferative properties but the mechanism of this effect remains incompletely understood. Following up on a recent observation in our laboratory that certain oxysterols bind with high affinity to the microsomal antiestrogen-binding site, we attempted to determine if a relationship existed between the antiproliferative effect of oxysterols and their binding affinities for the antiestrogen-binding site. Using the human breast cancer cell line, MCF7, and 14 different compounds (4 nonsteroidal antiestrogens, 6 oxysterols with appreciable binding affinities for the antiestrogen-binding site, and 4 other sterols with little or no affinity for this site), we showed that for compounds which bound to the antiestrogen-binding site, there was a clear positive correlation between their relative cytotoxic potencies and their affinities for this binding site. Two sterols, namely 25-hydroxycholesterol and 20 alpha-hydroxycholesterol, were exceptions to this general pattern, both clearly inhibited cell proliferation without having significant binding affinity for the antiestrogen-binding site. The same general order of antiproliferative potency of the oxysterols seen with MCF7 cells was also observed with the murine lymphoma cell line EL4. These findings suggest the possibility that the antiestrogen-binding site may be involved in mediating the antiproliferative effects of nonsteroidal antiestrogens and oxygenated sterols.

Animals↗
PubMed1991

Uptake of liposomes by cultured mouse bone marrow macrophages: influence of liposome composition and size.

A wide range of liposome compositions have previously been examined in vivo for their ability to affect the uptake of liposomes into cells of the reticuloendothelial (RE, mononuclear phagocyte) system (Allen, T.M. and Chonn, A. (1987) FEBS Lett. 223, 42-46; Allen et al. (1989) Biochim. Biophys. Acta 981, 27-35). In this study we have examined the ability of cultured murine bone marrow macrophages to endocytose liposomes of various compositions and have looked for correlations between the in vivo and the in vitro observations. Compounds which substantially decreased RE uptake of liposomes in vivo, such as monosialoganglioside (GM1) and a novel synthetic lipid derivative of polyethyleneglycol (PEG-PE), also greatly decreased liposome uptake by bone marrow macrophages in a concentration-dependent manner. Lipids which increase bilayer rigidity, such as sphingomyelin (SM) and cholesterol (CHOL), decreased both in vivo and in vitro uptake of liposomes. Likewise, positive correlations were observed between the in vivo behavior of liposomes containing phosphatidylserine (PS) or various gangliosides and the ability of these liposomes to be taken up by bone marrow macrophages. Total liposome uptake by macrophages increased with incubation time at 37 degrees C while very little liposome association with the macrophages was observed at 4 degrees C. Liposome uptake increased with liposome concentration and for liposomes composed of egg phosphatidylcholine (PC) uptake plateaued at 40 nmol lipid per mg cell protein. There was an inverse correlation between liposome size of extruded large unilamellar vesicles and their uptake by macrophages.

Animals↗
PubMed1991

Evaluation of three silicone-based materials as potential retrograde fillings in surgical endodontics.

Endodontic therapy has played an important role in maintaining the integrity of the natural dentition as a fully functional and esthetic masticatory apparatus. Although the sealing of the root canal system is usually accomplished by the conservative endodontic approach, cases which have failed or which involve perforations, broken instruments, or post-crown restorations are almost always treated surgically by using zinc-free amalgam as a retrograde filling material. However, the literature is controversial concerning the health risks and benefits of this material. For this reason, the study presented here was initiated to evaluate the potential of (a) a medical grade silicone-titanium mesh compound; (b) Endo-Fill (Lee Pharmaceuticals, El Monte, CA); and (c) an experimental expanding Endo-Fill (Lee Pharmaceuticals) as alternatives to amalgam. The three silicone-based materials and amalgam were compared for linear apical dye leakage. The leakage study involved 80 teeth which were instrumented, obturated, and prepared surgically for one of the four test materials. Either the teeth were placed immediately into 1% methylene blue dye or the material was allowed to set for 24 h before placement into the dye. Endo-Fill showed significantly less leakage than did the other materials in both the immediately placed and the 24-h set groups. On the other extreme, the experimental expanding Endo-Fill allowed significantly more dye penetration than did amalgam and the other silicone variations.

Bicuspid↗
PubMed1991

Effects of methotrexate on RNA and purine synthesis of astrocytes in primary culture.

There is increasing evidence to indicate that astrocytes are primary targets for methotrexate (MTX) neurotoxicity. However, the mechanism by which MTX exerts its deleterious effect on astroglial cells is not known. Methotrexate acts by inhibiting dihydrofolate reductase and in other cell systems has been reported to inhibit thymidylate synthesis, purine synthesis or both. To determine the mechanism involved in MTX-induced toxicity to the nervous system, RNA synthesis was studied in two week-old primary astrocyte cultures by measuring [3H]Uridine (Urd) incorporation 24 hours after exposure to varying concentrations of MTX. De novo purine synthesis was also studied by measuring incorporation of [14C]glycine and [14C]formate in cultured astrocytes. The radioactivity level of incorporated Urd in culture decreased to 48%, 53% and 43% after exposure to 1, 10 and 100 microM MTX. Total [14C]glycine incorporation was not affected while incorporation of [14C]formate was almost completely inhibited by MTX. The MTX-induced inhibition of [3H]Urd incorporation was not reversed by concomitant addition of exogenous purine bases (1 and 10 microM adenine, guanine and hypoxanthine) or nucleosides (1 and 10 microM adenosine, guanosine and inosine) to the MTX-treated cultures. On the other hand, addition of formyl-tetrahydrofolate reversed the MTX-induced reduction in [3H]Urd incorporation, indicating that the RNA inhibition was due to depletion of folate-dependent substrates for purine synthesis. Our results provide evidence that inhibition of purine and RNA synthesis may be the underlying mechanism involved in MTX-induced injury to the astrocytes, and may be important in the pathogenesis of MTX encephalopathy.

Animals↗
PubMed1991

Intracellular signaling pathway of endothelin-1.

The intracellular signaling pathway of endothelin-1 (ET-1) was studied in individual mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) using microspectrofluorimetry of fura-2 ([Ca2+]i), SPQ ([Cl-]i), and bisoxonol (membrane potential). ET-1 elicited a five-fold increase in [Ca2+]i that showed immediate and sustained phases. Both the Ca(2+)-free medium and nifedipine pretreatment curtailed the sustained phase of the response to ET-1. ET-1 resulted in sustained membrane depolarization of MCs and VSMCs. This depolarization was not attributed to Na influx, as Na-free medium did not abolish it. A Cl(-)-channel inhibitor, IAA-94, blunted the depolarization and sustained elevation of [Ca2+]i in response to ET-1. In aortic rings, both nifedipine and IAA-94 attenuated ET-1-induced contraction. No additivity in the effect of nifedipine and IAA-94 was detected. Studies of SPQ fluorescence changes induced by ET-1 revealed an immediate and sustained increase in fluorescence intensity consistent with the decrease in [Cl-]i. The sustained but not immediate increase in SPQ fluorescence was virtually abolished in Ca(2+)-free medium with or without pretreatment with the intracellular Ca2+ chelator BAPTA. In conclusion, we hypothesize that ET-1 results in Ca2+ mobilization and Ca(2+)-dependent and -independent activation of Cl- channels. Ensuing Cl- efflux causes membrane depolarization and, in turn, activation of voltage-gated Ca2+ channels in MCs and VSMCs. The latter results in sustained elevation of [Ca2+]i that is indispensable for the full-scale contractile response to ET-1.

Animals↗
PubMed1991

Role of endothelin in the development of Dahl hypertension.

To evaluate the possible role of endothelin in the development and/or maintenance of hypertension in Dahl rats, we examined the responsiveness of isolated vascular smooth muscle and glomerular mesangial cells, as well as deendothelialized vascular ring preparations to endothelin-1 (ET-1). Production of immunoreactive endothelin (ir-ET) was studied in freshly isolated glomeruli and renal medullary slices. Both glomerular mesangial cells and vascular smooth muscle cells obtained from prehypertensive Dahl-S rats exhibited an exaggerated [Ca2+]i response to ET-1, as compared with cells obtained from Dahl-R rats. This was paralleled by the enhanced isometric contraction of vascular rings obtained from prehypertensive Dahl-S rats. ir-ET production was doubled in response to 0.1 mM ouabain in tissue samples obtained from prehypertensive Dahl-S, but not Dahl-R rats. This effect was not observed in tissues obtained from animals fed a 4% NaCl diet (hypertensive). Immunocytochemistry of ET distribution in the outer medullary stripe showed approximately a 40% higher fluorescence intensity in sections obtained from Dahl-S rats fed 4% NaCl diet as compared with Dahl-R rats fed the same diet. Northern blot analysis of poly(A)+ RNA extracted from medullae of prehypertensive Dahl-S and -R rats using a full-length cDNA probe for rat ET-1 revealed a marginal induction of pre-pro-ET-1 message in Dahl-S samples after 30 and 60 min of incubation with 0.1 mM ouabain. In conclusion, increased responsiveness of target cells to ET-1 and inducibility of ir-ET production in prehypertensive Dahl-S rats are in favor of a possible role of this peptide in the pathogenesis of Dahl hypertension. We hypothesize that ouabain-like factor(s) may trigger production of ET, thus serving as a link between high-salt intake and the development of hypertension in Dahl-S rats.

Animals↗
PubMed1991

Case-control study of cigarette smoking and primary hepatoma in an aflatoxin-endemic region of China: a protective effect.

Aflatoxin is believed to be a major causative agent in the high incidence of primary liver cancer seen in certain regions of the world. In Fujian Province, an aflatoxin-endemic region of China, we compared the cigarette smoking habits of 200 primary hepatoma patients with those of 200 matched nonhepatoma controls. We excluded from our study all individuals with evidence of hepatitis B virus serum antigen and/or alcoholic cirrhosis. Interestingly, two groups of hepatoma patients could be discerned. In patients more than 50 years of age, a significantly higher number of cases of primary hepatoma was found among nonsmokers than smokers (odds ratio = 2.06; 95% confidence interval = 1.32-3.20). In patients less than 50 years of age, this difference was not seen. Previous studies in the rat, mouse and duck had suggested that agents present in cigarette smoke might induce a cytochrome P450-mediated detoxication pathway, leading to protection against aflatoxin-induced primary liver cancer. Our clinical data in the present study are therefore consistent with the previous laboratory animal experiments.

Adult↗
PubMed1991

Dynamics of creatine kinase shuttle enzymes in the human heart.

Myocardial cytoplasmic creatine kinase subunits M and B, mitochondrial CK (CKMIT), and citrate synthase (CS) were determined in 10 locations of the normal human heart (n = 8) and in papillary muscles of patients operated on for mitral regurgitation (n = 6). Compared to atrial biopsies, septal and left ventricular biopsies showed higher activities for CS (P less than 0.0001), total CK (P less than 0.05) and CKMIT (P less than 0.0001). CKM was evenly distributed. CKB activity in the right septum and left ventricular locations were 0.5-1% of total CK and 4-5 times lower than those of the atria and the right ventricular free wall. Activities of CS, CKB and CKMIT in right septal biopsies did not differ from those in left ventricular locations. The activities of CS, total CK, and CKM in papillary muscle from patients operated on for mitral regurgitation did not differ from that of healthy papillary muscle. CKMIT was about 40% lower (P less than 0.02), whereas CKB was 15-20 times higher (P less than 0.0001) than in the healthy heart. In conclusion, adaptations within the creatine kinase system occur in the human heart in health and disease. Small amounts of CKB in the normal left ventricle, as opposed to the right ventricular free wall, might be related to differences in myocardial perfusion during the cardiac cycle. In disease, a decreased CKMIT and dramatically increased CKB may indicate a stressed intracellular energy transfer. CK enzyme activities in right septal biopsy specimens may be used as an indication of metabolic stress on the myocardium of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

DNA typing for HLA-DR, and -DP alleles in a Chinese population using the polymerase chain reaction (PCR) and oligonucleotide probes.

We have determined alleles of HLA-DRB1, DRB3, DRB5, DQA1, DQB1, and DPB1 loci in 91 unrelated healthy individuals from North China. Group-specific PCR primers were employed for the analysis of subsets of DR1, DR2, DR4, DRw52, and DPB. With allele-specific probes, 22 DRB1, 8 DQA1, 13 DQB1, and 12 DPB1 alleles were found in this panel. Allele frequencies showed that 25.3% of the subjects had DR7 and 26.4% had DR9, only 5.5% had DRB1*0301 (DRw17). In the DR4 group, DRB1*0405 (Dw15, 8.8%) and 0406 (KT2, 9.9%) were the most prevalent alleles. DRB1*0404 (Dw14.1), 0407 (Dw13.2) and 0408 (Dw14.2) were absent and the other alleles of the DR4 group were rare. The most common DRw6 subset was DRB1*1401 (8.8%). DRB1*0802 and 0803 were present (2.2%, 6.6%), and DRB1*0801 was not found. Associations with DQA1 and DQB1 were generally similar to those found in other populations. DPB1*0501 was the most frequent (60.2%) allele at the DPB1 locus. Overall our study shows that the distribution of class II alleles in a population from Mainland China is quite different from other ethnic groups. The high frequency of the KT2 subset of DR4. (DRB1*0406) and of DPB1*0501 are the most striking features found. A new type of DR4 was determined in one subject. It was like DR4-Dw15 (DRB1*0405) but, according to our hybridization patterns, it encoded valine instead of glycine in position 86. It is now called DRB1*0410.

Alleles↗
PubMed1991

Saturable binding of anesthetics to nicotinic acetylcholine receptors. A possible mechanism of anesthetic action.

Recent controversies in the existence of saturable binding of general anesthetics in brain tissues prompted a careful examination of specific binding of anesthetics to neural receptors. We examined the binding of both local and general anesthetics using electron spin resonance and radioligand criteria. Our results suggested that the hydrophobic path, most probably through the lipid bilayer, figures importantly in the binding of the uncharged moieties of anesthetics. Competitive interactions by hydrophobic compounds for the high-affinity site in the nicotinic acetylcholine receptor led us to propose a hypothesis that includes a hydrophobic crevice of limited volume as part of the high-affinity site. Association of anesthetic at this crevice is in turn dependent on the anesthetic concentration in the lipid phase of the membrane. The hypothesis provides a mechanism for the saturable interaction of anesthetics with their protein target site in the membrane without violating the correlations expressed by the Meyer-Overton rule of anesthetic action.

Anesthesia↗
PubMed1991

Intracellular ramification of endothelin signal.

Effects of porcine 1-21 endothelin (ET-1) on [Ca2+]i, [Na+]i, and [Cl-]i and on membrane potential were studied in individual mesangial (MC) and vascular smooth muscle (VSMC) cells using microspectrofluorimetry of fura-2, SBFI, SPQ, and bis-oxonol, respectively. ET-1 increased [Ca2+]i by fivefold, showing an immediate and a sustained phase of response. Ca(2+)-free medium and nifedipine pretreatment significantly curtailed the sustained phase of response to ET-1. These findings were confirmed in studies of vascular ring preparations, demonstrating that Ca2+ influx may account for at least 50% of contraction. ET-1 caused immediate and sustained depolarization of MC and VSMC. This could not be attributed to Na+ influx, since fluorescence of SBFI was not affected by ET-1 and Na(+)-free medium did not abolish the ET-1-induced membrane depolarization. Studies of SPQ fluorescence changes induced by ET-1 revealed an increase in fluorescence intensity consistent with the decrease in [Cl-]i. A Cl- channel blocker, IAA-94, abolished changes in SPQ fluorescence and curtailed sustained phases of membrane depolarization and [Ca2+]i elevation in response to ET-1, but did not affect KCl-induced [Ca2+]i transients. IAA-94 also attenuated the ET-1-induced contraction of aortic rings. Microinjection of either calcium gluconate or inositol 1,4,5-trisphosphate (IP3) in SPQ-loaded cells resulted in an increase in fluorescence mimicking the effect of ET-1. These changes were blunted by pretreatment of cells with BAPTA and incubation in Ca(2+)-free medium. When IP3 was microinjected into fura-2-loaded MC, this resulted in immediate and sustained elevation of [Ca2+]i. In conclusion, generation of IP3 results in mobilization of intracellular Ca2+ stores and activation of Cl- channels. Ensuing Cl- efflux causes membrane depolarization and, in turn, activation of voltage-dependent Ca2+ channels, resulting in sustained elevation of [Ca2+]i which is indispensable for the full-scale contraction produced by ET-1.

Animals↗
PubMed1991

Role of prostanoids in renin-dependent and renin-independent hypertension.

We investigated the role of prostanoid-mediated pressor mechanisms in setting the level of blood pressure in renin-dependent and renin-independent models of hypertension in unanesthetized rats. Intravenous administration of a blocker of thromboxane A2/prostaglandin endoperoxide receptors, SQ29548 (2 mg/kg bolus injection plus 2 mg/kg/hr for 3 hours), reduced from 162 +/- 4 to 144 +/- 5 mm Hg (p less than 0.05) the blood pressure of rats with aortic coarctation-induced hypertension at 7-14 days after coarctation when plasma renin activity is greatly increased. In contrast, treatment with SQ29548 was without effect on the blood pressure of either normotensive or hypertensive rats (i.e., aortic coarctation-induced hypertension at 90-113 days after coarctation, deoxycorticosterone-salt-induced hypertension) having normal or depressed values of plasma renin activity. The blood pressure-lowering effect of SQ29548 in the early phase of aortic coarctation-induced hypertension was positively correlated with the prevailing plasma renin activity and could not be demonstrated in hypertensive rats pretreated with indomethacin. We attribute the hypotensive effect of SQ29548 to interference with pressor mechanisms that depend on activation of thromboxane A2/prostaglandin endoperoxide receptors and suggest that such prostanoid-mediated mechanisms are operational and contribute to an increase in blood pressure in angiotensin-dependent forms of hypertension. Also prostanoid-mediated vasodepressor mechanisms are operational in the early phase of aortic coarctation-induced hypertension since the blood pressure of rats pretreated with SQ29548 was increased by the subsequent administration of indomethacin. Accordingly, the blood pressure of rats with aortic coarctation-induced hypertension is influenced by the interplay of prostanoid-mediated pressor and vasodepressor mechanisms.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Role of endothelium-derived prostanoid in angiotensin-induced vasoconstriction.

To test the hypothesis that prostanoids contribute to angiotensin II-induced vascular contraction, we compared the effect of angiotensin II on isometric tension development by rings of descending thoracic aorta bathed in Krebs' bicarbonate buffer with and without indomethacin (10 microM) to inhibit cyclooxygenase, CGS13080 (10 microM) to inhibit thromboxane A2 synthesis, or SQ29548 (1 microM) to block thromboxane A2/prostaglandin endoperoxide receptors. The comparisons were made in rings of aorta taken from normotensive rats and from rats with aortic coarctation-induced hypertension at 12 days and 90-113 days after coarctation. These rings released thromboxane B2, which was found to be endothelium dependent, increased in hypertensive rats, and stimulated by angiotensin II (10(-6) M) in normotensive rats and in hypertensive rats at 12 days after coarctation. The angiotensin II (10(-6) to 10(-5)M)-induced contraction of aortic rings was increased by about 30% at 12 days after coarctation and decreased at 90-113 days after coarctation. Removal of the endothelium increased the contractile effect of angiotensin II (10(-6) M) in aortic rings of normotensive rats and hypertensive rats at 90-113 days after coarctation but decreased the effect in aortic rings of hypertensive rats at 12 days after coarctation. In rats at 12 days after coarctation, the angiotensin II (10(-6) M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080. These data suggest that a prostanoid-mediated and endothelium-dependent mechanism of vasoconstriction contributes to the constrictor effect of angiotensin II in aortic rings of rats in the early phase of aortic coarctation-induced hypertension.

Acetylcholine↗
PubMed1991

Arachidonic acid elicits endothelium-dependent release from the rabbit aorta of a constrictor prostanoid resembling prostaglandin endoperoxides.

This study was designed to investigate the mediator(s) of endothelium-dependent arterial constrictor responses evoked by arachidonic acid in vitro. A segment of descending rabbit thoracic aorta was isolated and perfused (1-2 ml/min) with oxygenated Krebs' bicarbonate buffer. Changes in the vascular smooth muscle-contracting activity of the aortic effluent were detected by superfusion bioassay using either strips of rabbit aorta or rings of dog saphenous vein, both denuded of endothelium and exposed to indomethacin (10 microM). Arachidonic acid (5-50 micrograms) injected into the inflow of the perfused aorta caused a dose-related increase in the vascular smooth muscle-contracting activity of the aortic effluent, whereas arachidonic acid added directly into the aortic effluent did not. The arachidonic acid-induced elevation of vascular smooth muscle-contracting activity in the aortic effluent was not apparent when indomethacin (10 microM) was added to the aortic inflow to inhibit cyclooxygenase, when the endothelium of the perfused aorta was removed by rubbing, or when the thromboxane A2/prostaglandin H2 receptors of the vascular tissues used for bioassay were blocked with an antagonist (1 microM SQ29548), and was unaffected when an inhibitor of thromboxane synthase (10 microM CGS 13080) was added to the aortic inflow. This effect of arachidonic acid was accompanied by release of prostaglandin H2 (measured as prostaglandin F2 alpha after reduction with SnCl2) in amounts sufficient to elicit contraction of the vascular tissues used for bioassay and was attenuated when a reducing agent (2 mM FeCl2) that converts prostaglandin H2 to 12-heptadecatrienoic acid was added to the aortic effluent. Collectively, these observations suggest that arachidonic acid stimulates endothelium-dependent release from the perfused aorta of a prostanoid that contracts vascular smooth muscle via interaction with thromboxane A2/prostaglandin H2 receptors. The study also suggests that the prostanoid responsible for the vascular smooth muscle-contracting activity of the aortic effluent is a prostaglandin endoperoxide(s) rather than thromboxane A2.

Animals↗