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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

At least 145 records · Page 8Linked to original sources
PubMed1997

Multiple antibiotic resistance (MAR) index and its reversion in Pseudomonas aeruginosa.

The MAR indexes of hospital isolates of Pseudomonas aeruginosa were determined with reference to nine different cephalosporins. The values for all the strains were higher than 0.2 suggesting their origin from a high risk source of contamination where antibiotics are often used. Emergence of MAR pathogenic strains of Ps. aeruginosa indicated possible nosocomial infection in the hospital environment. beta-Lactamases produced by these organisms were tested and their inhibition by clavulanic acid was studied. beta-Lactamase produced by one of these strains (Ps-1) could not be inhibited by clavulanic acid whereas beta-lactamases of three other strains (Ps-2, Ps-3 and Ps-4) could be inhibited by clavulanic acid in the presence of cephalosporins, suggesting a possible use of clavulanic acid in combination with cephalosporins, to combat beta-lactamase induced resistance in Ps. aeruginosa.

Anti-Bacterial Agents↗
PubMed1997

Regulating the use of degraded oil/fat in deep-fat/oil food frying.

During frying, the degradation of oil produces harmful compounds. Improper monitoring of oil-discard times in restaurants either risks the public health or causes financial losses to industries. Measuring the oil quality is a complex problem and an online sensor is needed. The process of frying reviewed includes moisture, heat and fat/oil transfer, crust formation and various structural, textural and chemical changes in the product, and degradation of frying medium. Some of the European nations and the U.S. have specific regulations against the use of deteriorated frying oils. Due to the absence of a suitable online frying oil quality sensor for restaurant situations, it is difficult to implement any regulation against the use of deteriorated frying oil. Based on various regulations, a model regulation to increase the safety and quality of fried foods is discussed. Background and requirements for developing an online sensor to measure frying oil quality are discussed. Other related areas reviewed in this article are factors affecting oil penetration and absorption by the food, surfactant theory of frying, analytical indices, quick tests and acceptability of frying oil.

Cooking↗
PubMed1997

Mycobacterial growth and sensitivity to H2O2 killing in human monocytes in vitro.

The intracellular growth and susceptibilities to killing by H2O2 in cultured human monocytes of a number of mycobacterial species including laboratory strains and clinical isolates of Mycobacterium tuberculosis, and Mycobacterium bovis bacillus Calmette-Guerin (BCG) and a clinical isolate of Mycobacterium avium-M. intracellulare were examined. The clinical isolate of M. avium-M. intracellulare did not replicate in freshly explanted monocytes (generation time of >400 h); BCG replicated with a generation time of 95 h, and M. tuberculosis strains CDC551, H37Rv, and H37Ra replicated with generation times of 24, 35, and 37 h, respectively, during the 4-day growth assay. When cultured in monocytes for 4 days, the mycobacteria were variably sensitive to H2O2-induced killing. A positive correlation between the generation time and percent killing of intracellular bacilli was observed. By comparison, mycobacterial strains were similarly sensitive to H2O2 treatment in cell-free culture media and in sonicated cell suspensions. Using a number of inhibitors of reactive oxygen intermediates we determined that other than catalase the inhibitors tested did not affect H2O2-induced killing of intracellular mycobacteria. Our studies suggest that the killing of mycobacteria growing in human monocytes in vitro by the addition of exogenous H2O2 is dependent on the susceptibility to a peroxide-induced killing pathway as well as on the intracellular growth rate of the mycobacteria.

Antioxidants↗
PubMed1997

Arrhythmias in women.

Implications for nurses caring for women with arrhythmias include maintaining close monitoring of the QTc interval when administering antiarrhythmic agents and frequent evaluation of patients on antihypertensive drugs, diuretics, and digoxin. Continuous ST segment monitoring should be implemented in female patients after MI. Nurses should serve as a patient advocate for appropriately timed aggressive therapy for the management of CAD or MI in women, comparable to that which would be offered to male patients in a similar clinical situation. ECG monitoring of pregnant patients is imperative if a history of arrhythmias or prolonged QTc is known or even suspected. Numerous research studies have been performed to evaluate the effects, dangers, complications, and contributing factors for cardiac arrhythmias in men and women. Few studies, however, have focused primarily on women in this area. Occasionally, studies may contain small secondary statements about gender differences, but in-depth research regarding arrhythmias if women is lacking. Furthermore, research findings vary among authors and often present conflicting information. Further studies are needed to evaluate the role of heart disease and arrhythmias in women and to determine if therapies for arrhythmias should be gender specific.

Arrhythmias, Cardiac↗
PubMed1996

ATP-dependent transport of lipophilic cytotoxic drugs by membrane vesicles prepared from MRP-overexpressing HL60/ADR cells.

MRP is an ATP-binding cassette family transporter that confers cellular resistance to a variety of natural product cytotoxic agents. However, the biochemical mechanism by which MRP confers resistance has not been established. To gain insight into its mechanism of action, the in vitro substrate specificity of MRP was examined by analyzing drug uptake into membrane vesicles prepared from MRP-overexpressing HL60/ADR cells. Compared to control HL60 membrane vesicles, HL60/ADR membrane vesicles exhibited markedly enhanced ATP-dependent transport of daunorubicin, etoposide, and vincristine. In contrast, little or no increased uptake was observed for vinblastine and Taxol. This pattern of in vitro substrate specificity was consistent with the analysis of the HL60/ADR drug resistance phenotype, which revealed substantial levels of resistance to anthracyclines, etoposide, and vincristine, but only slightly increased resistance to vinblastine and Taxol. Drug transport into HL60/ADR membrane vesicles was osmotically sensitive and dependent on ATP concentration, with a K(m) value of 45 microM for ATP. Lineweaver-Burk analysis indicated that substrate transport was concentration-dependent, with apparent K(m) values of 6.1, 5.7, and 5.5 microM for daunorubicin, etoposide, and vincristine, respectively. The P-glycoprotein-modulating agents cyclosporin A, PSC833, and verapamil, which have modest reversing effects on MRP-overexpressing cell lines, were weak competitive inhibitors of daunorubicin transport, with Ki values of 35, 84, and 95 microM, respectively. In addition, the glutathione analog azidophenacyl-glutathione, oxidized glutathione, and the LTD4 antagonist MK571 were competitive inhibitors of daunorubicin transport with Ki values of 69, 31, and 3.0 microM, respectively. Genistein, an MRP-specific modulating agent, and arsenate, a compound for which MRP has previously been reported to confer resistance, were also competitive inhibitors, with Ki values of 17 and 29 microM, respectively. These results are consistent with a previous report in which we demonstrated that HL60/ADR membrane vesicles transport azidophenacylglutathione and that transport of this agent is competitively inhibited by daunorubicin, vincristine, and etoposide [Shen et al., (1966) Biochemistry 35, 5719-5725]. Together, these uptake studies performed with HL60/ADR membrane vesicles constitute a consistent body of evidence that indicates that MRP transports both glutathione S conjugates and unaltered natural product drugs and support the idea that the direct transport of unaltered lipophilic cytotoxic drugs is the predominant biochemical mechanism whereby MRP confers multidrug resistance.

ATP-Binding Cassette Transporters↗
PubMed1996

Structure and in vitro substrate specificity of the murine multidrug resistance-associated protein.

MRP is a recently described ATP-binding cassette transporter that confers cellular resistance to natural product cytotoxic drugs. To examine the biochemical activity and cellular physiology of this transporter, we isolated the murine MRP homologue and analyzed its in vitro substrate specificity. Murine MRP transcript is widely expressed in tissues and encodes a protein of 1528 amino acids that is 88% identical to its human homologue. Hydropathy analysis indicated that murine and human MRP, the yeast cadmium resistance transporter and the sulfonylurea receptor share a conserved topology distinguished from P-glycoprotein and the cystic fibrosis conductance regulator by an N-terminal hydrophobic region that contains several potential transmembrane domains. Drug uptake assays performed with membrane vesicles prepared from NIH3T3 cells transfected with a murine MRP expression vector revealed ATP-dependent transport for the natural product cytotoxic drugs daunorubicin and vincristine, as well as for the glutathione S-conjugates leukotriene C4 and azidophenacyl-S-glutathione. Drug transport was osmotically sensitive and saturable with regard to drug and ATP concentrations, with K(m) values of 19 microM, 19 microM, 26 nM, 17 microM, and 77 microM for daunorubicin, vincristine, leukotriene C4, APA-SG, and ATP, respectively. Consistent with broad substrate specificity, the drug glutathione conjugate APA-SG, oxidized glutathione, the LTD4 antagonist MK571, arsenate, and genistein were competitive inhibitors of daunorubicin transport, with Ki values of 32 microM, 25 microM, 1.9 microM, 108 microM, and 23 microM, respectively. This study demonstrates that the substrate specificity of murine MRP is quite broad and includes both the neutral or mildly cationic natural product cytotoxic drugs and the anionic products of glutathione conjugation. The widespread expression pattern of murine MRP in tissues, combined with its ability to transport both lipophilic xenobiotics and the products of phase II detoxification, indicates that it represents a widespread and versatile cellular defense mechanism.

3T3 Cells↗
PubMed1996

Efficient vasoactive intestinal polypeptide hydrolyzing autoantibody light chains selected by phage display.

An immunoglobulin light chain (L chain) library derived from the peripheral blood lymphocytes of a patient with asthma was cloned into a phagemid vector. Phage particles displaying L chains capable of binding vasoactive intestinal polypeptide (VIP) were isolated by affinity chromatography. Two VIP binding L chains were expressed in Escherichia coli in soluble form and purified to electrophoretic homogeneity by metal chelating and protein L affinity chromatography. Both L chains catalyzed the hydrolysis of [tyr10-125I]VIP substrate. The catalytic activity eluted at the molecular mass of the monomer form of the L chain (28 kDa) from a gel filtration column. The activity was bound by immobilized anti-kappa-chain antibody. A control recombinant L chain displayed no catalytic activity. Hydrolysis of VIP by the catalytic L chains was saturable and consistent with Michaelis-Menten kinetics. The turnover of the L chains was moderate (0.22 and 2.21/min) and their Km values indicated comparatively high affinity recognition of VIP[111 and 202 nM), producing catalytic efficiencies comparable to or greater than trypsin. Unlike trypsin, the L chains did not display detectable cleavage of casein, suggesting a catalytic activity specialized for VIP. Comparisons of the nucleotide sequences of the L chain cDNA with their putative germ-line counterparts suggested the presence of several replacement mutations in the complementarity determining regions (CDRs). These observations suggest: (a) Retention or acquisition of catalytic activity by the L chains is compatible with affinity maturation of antibodies; and (b) The autoimmune L chain repertoire can serve as a source of substrate-specific and efficient catalysts.

Amino Acid Sequence↗
PubMed1996

ATP-dependent uptake of natural product cytotoxic drugs by membrane vesicles establishes MRP as a broad specificity transporter.

MRP is a recently isolated ATP-binding cassette family transporter. We previously reported transfection studies that established that MRP confers multidrug resistance [Kruh, G. D., Chan, A., Myers, K., Gaughan, K., Miki, T. & Aaronson, S. A. (1994) Cancer Res. 54, 1649-1652] and that expression of MRP is associated with enhanced cellular efflux of lipophilic cytotoxic agents [Breuninger, L. M., Paul, S., Gaughan, K., Miki, T., Chan, A., Aaronson, S. A. & Kruh, G. D. (1995) Cancer Res. 55, 5342-5347]. To examine the biochemical mechanism by which MRP confers multidrug resistance, drug uptake experiments were performed using inside-out membrane vesicles prepared from NIH 3T3 cells transfected with an MRP expression vector. ATP-dependent transport was observed for several lipophilic cytotoxic agents including daunorubicin, etoposide, and vincristine, as well as for the glutathione conjugate leukotriene C4 (LTC4). However, only marginally increased uptake was observed for vinblastine and Taxol. Drug uptake was osmotically sensitive and saturable with regard to substrate concentration, with Km values of 6.3 microM, 4.4 microM, 4.2 microM, 35 nM, and 38 microM, for daunorubicin, etoposide, vincristine, LTC4, and ATP, respectively. The broad substrate specificity of MRP was confirmed by the observation that daunorubicin transport was competitively inhibited by reduced and oxidized glutathione, the glutathione conjugates S-(p-azidophenacyl)-glutathione (APA-SG) and S-(2,4-dinitrophenyl)glutathione (DNP-SG), arsenate, and the LTD4 antagonist MK571. This study establishes that MRP pumps unaltered lipophilic cytotoxic drugs, and suggests that this activity is an important mechanism by which the transporter confers multidrug resistance. The present study also indicates that the substrate specificity of MRP is overlapping but distinct from that of P-glycoprotein, and includes both the neutral or mildly cationic natural product cytotoxic drugs and the anionic products of glutathione conjugation. The widespread expression of MRP in tissues, combined with its ability to transport both lipophilic xenobiotics and the products of phase II detoxification, indicates that the transporter represents a widespread and remarkably versatile cellular defense mechanism.

3T3 Cells↗
PubMed1996

Cellular and in vitro transport of glutathione conjugates by MRP.

MRP is a recently identified ATP-binding cassette transporter. We previously established that MRP confers resistance to a spectrum of natural product cytotoxic drugs [Kruh, G.D., (1994) Cancer Res. 54, 1649-1652], that expression of MRP is associated with enhanced drug efflux [Breuninger, L.M., (1995) Cancer Res. 55, 5342-5347], and that MRP transcript is widely expressed in human tissues and solid tumor cell lines [Kruh, G.D., (1995) J. Natl. Cancer Inst. 87, 1256-1258]. In the present study the relationship between MRP and drug glutathione S-conjugates was examined. We observed that MRP was labeled by azidophenacylglutathione (APA-SG), a photoaffinity analog of glutathione, and that inside-out membrane vesicles prepared from MRP-overexpressing HL60/ADR cells transported this compound. Transport into membrane vesicles was ATP-dependent, sensitive to osmolarity, and saturable with regard to APA-SG and ATP concentrations, with Km values of 15 and 61 microM, respectively. APA-SG transport was competitively inhibited by the natural product cytotoxic drugs daunorubicin, vincristine, and etoposide, with Ki values of 4.8, 3.8, and 5.5 microM, respectively. Oxidized glutathione, the drug-glutathione S-conjugate DNP-SG, the LTD4 antagonist MK571 and arsenate were also competitive inhibitors, with Ki values of 9.0, 23.4, 1.1, and 15.0 microM, respectively. Analysis of the fate of monochlorobimane in MRP transfectants revealed reduced intracellular concentrations of drug-glutathione S-conjugates associated with enhanced efflux and altered intracellular distribution. These results indicate that MRP can transport glutathione conjugates in vitro and in living cells and suggest the possibility that the transporter may represent a link between cellular resistance to some classes of cytotoxic drugs and glutathione-mediated mechanisms of resistance. In addition, the observation that both mildly cationic or neutral natural product cytotoxic drugs and anionic compounds such as DNP-SG, MK571, and arsenate are competitive inhibitors of MRP action suggests that the substrate specificity of the transporter is quite broad.

3T3 Cells↗
PubMed1996

Gender difference in analgesic response to the kappa-opioid pentazocine.

Gender difference in analgesia produced by the kappa-opiate pentazocine was investigated in a model of post-operative dental pain. In a recent study [Gordon et al., Neuroscience, 69 (1995) 345-349.] evaluating interaction between the GABAB agonist baclofen and opiates with respect to postoperative analgesia we found that females receiving pentazocine for the treatment of postoperative pain showed better analgesia than did males receiving similar treatment. To follow-up this result, we evaluated for the effect of gender on analgesia produced by pentazocine administered to participants not receiving another experimental medication. The analgesic response to pentazocine in ten females was compared to that in eight males. All participants were administered pentazocine after undergoing surgery for the removal of impacted third molars. We confirm our previous finding that pentazocine produces significantly greater analgesia in females than in males; no significant difference was observed in analgesia among females in different phases of the menstrual cycle.

Adult↗
PubMed1996

Natural catalytic antibodies.

Catalytic activity can arise by natural means in antibodies. Several naturally-occurring peptides and synthetic protease substrates are known to be cleaved by antibodies. There is an increased production of antigen-specific catalytic antibodies in autoimmune disease. Antibody light chains isolated from multiple myeloma patients frequently express proteolytic activity. Immunization protocols using as antigens the ground state of a naturally-occurring polypeptide, transition state analogs or anti-enzyme antibodies are known to provoke catalytic antibody synthesis. Active site residues in the light chain subunit serve as the catalytic residues in an antibody with peptide bond cleaving activity. Mutagenesis in the active site can potentially generate improved catalysts. The possible mechanisms underlying proteolysis by natural antibodies and evolution of the catalytic activity are reviewed.

Animals↗
PubMed1996

Regulation of actin and tubulin gene expression by thyroid hormone during rat brain development.

In the developing brain the active neurite outgrowth during the early phase of synaptogenesis is associated with a thyroid hormone dependent expression of tubulin and actin. In this study, the molecular mechanism of thyroid hormone (TH) action on actin and tubulin gene expression in the developing rat brain has been investigated by comparing the steady state levels of both mRNAs with their respective rates of transcription in cerebra from normal and hypothyroid animals. The developmental profile of actin as well as tubulin mRNAs in both normal and hypothyroid brains display a biphasic pattern, increasing progressively during the first week after birth and declining thereafter. However, hypothyroidism resulted in a significant reduction in the steady state levels of both mRNAs during the first postnatal week. During the second and third weeks, in contrast to their rapid decline in the normal controls, the corresponding decrease in the hypothyroid cerebra was retarded and prolonged resulting in their higher levels under TH-deficient condition. Kinetics of stimulation of actin and tubulin mRNAs in the 5-day hypothyroid cerebra following injection of the optimal dose of TH (200 micrograms T3/100 g body wt.) demonstrated elevation of both mRNAs within 1 h indicating a possible role of TH at the transcriptional level. In vitro transcription experiments by nuclear run off assay unambiguously confirmed that actin gene transcription is depressed in the hypothyroid cerebra compared to normal control. This reduced rate of transcription could be significantly induced in the hypothyroid cerebra by incubation of hypothyroid nuclei with T3 prior to transcription. In contrast, except for a reduced transcription in 5-day hypothyroid nuclei, no effect on tubulin gene transcription was evident at any other age. Moreover preincubation of hypothyroid nuclei from all three ages with T3 had no stimulatory effect on tubulin gene transcription. Analysis of age related changes in the rates of transcription of actin and tubulin genes with their corresponding steady state mRNA levels in normal and hypothyroid developing brain provides strong evidence that although additional modes of regulation may be operative, transcription represents an important level of control for thyroidal regulation of actin gene expression while tubulin gene expression is primarily regulated at post-transcriptional level.

Actins↗
PubMed1996

Comparable growth of virulent and avirulent Mycobacterium tuberculosis in human macrophages in vitro.

The relative virulence and avirulence of Mycobacterium tuberculosis strains H37Rv and H37Ra were previously defined using animal infection models. To investigate host species' specificity of mycobacterial virulence, growth of the 2 M. tuberculosis strains in human monocyte-derived macrophages in vitro was studied. Mycobacterial growth was evaluated by acid-fast staining, electron microscopy, and colony-forming units (cfu) assay. As expected, the 2 strains demonstrated significantly different growth rates in mouse macrophages in vitro (53 h for H37Rv, 370 h for H37Ra). In marked contrast, in human macrophages the average division times of the strains were nearly equal (80 h for H37Rv and 76 h for H37Ra by cfu measurement, and 96 h for H37Rv and 104 h for H37Ra by acid-fast staining). These findings indicate that observations of mycobacterial virulence in murine systems may not necessarily translate to the human system, in which different mechanisms to control mycobacterial growth may be expressed.

Animals↗
PubMed1996

Dietary habits of gallstone patients in Northern India.

Dietary intake and plasma lipids were estimated in 200 patients with gallstones and 98 control subjects from a hospital in Northern India and were matched for age, sex, and social class. The intake of total calories and carbohydrates and the plasma triglyceride values were higher in all gallstone patients as compared with controls (p < 0.05 and p < 0.01, respectively). The dietary intake of refined carbohydrates was higher than in controls, but only in the female patients with gallstones (35.6 +/- 32.9 g/day compared with 24.5 +/- 11.8 g/day; p < 0.001). By contrast, the male patients with gallstones had an increased intake of fat (patients 79.0 +/- 38.1 g/day vs. controls 60.2 +/- 24.3 g/day; p < 0.05) and had increased plasma cholesterol values (patients 166.4 +/- 54.2 mg/dl vs. controls 140.3 +/- 32.8 mg/dl; p < 0.01). Such sex differences in the dietary intake and plasma lipid values may form a special feature of gallstone disease in Northern India and should be studied further.

Adult↗
PubMed1996

Role of thyroid hormone in the morphological differentiation and maturation of astrocytes: temporal correlation with synthesis and organization of actin.

Morphological changes and the molecular mechanisms associated with the maturation of astrocytes were studied under normal and thyroid hormone-deficient conditions using long-term (30 days) primary cultures derived from the neonatal rat brain. Immunocytochemical staining of cells with a monoclonal antibody specific to glial fibrillary acidic protein demonstrated for the first time that, similar to their maturation in vivo, astrocytes maintained in normal serum-containing medium can undergo complete maturation involving two distinct stages of morphological differentiation (from radial glia to flat polygonal cells with epithelioid morphology and then to mature process-bearing cells with stellate morphology). Deficiency of thyroid hormone delays the first step and totally blocks the second stage of differentiation in the maturation process. Comparative staining of normal and thyroid hormone-deficient astrocytes with filamentous actin-specific fluorescein isothiocyanate-phalloidin and quantitation of the various forms of intracellular actin using an improved DNase I assay demonstrated that maturation of astroglial cells is associated with characteristic alterations in the level of cytoskeletal and noncytoskeletal filamentous (F) actin. In particular, the maintenance of the epithelioid form of the hypothyroid astrocytes is associated with a progressive increase in the level of cytoskeletal F-actin and a concomitant decline in the level of non-cytoskeletal F-actin. Quantitation of actin mRNA by Northern blot analysis and studies on the rate of actin synthesis at various stages of differentiation showed that the initial transformation into the epithelioid form is associated with an increase in the rate of synthesis of actin and the expression of its mRNA, while the final transformation into the nature process-bearing form is correlated with a decline in these parameters. The results indicates that thyroid hormone plays an obligatory role in promoting the differentiation and maturation of astrocytes, and that during this process the hormone regulates the expression of actin and its intracellular organization in a way conducive to morphological differentiation.

Actins↗
PubMed1996

H2O2 induces monocyte apoptosis and reduces viability of Mycobacterium avium-M. intracellulare within cultured human monocytes.

Mycobacterium avium-M. intracellulare, an intracellular parasite of mononuclear phagocytes, rarely causes disease in immunocompetent individuals. In contrast, in human immunodeficiency virus type 1-infected patients, M. avium-M. intracellulare can infect almost every tissue and organ. This suggests that immunocompetent individuals have a protective mechanism to control or prevent the infection. How mycobacterial may be killed by the host immune response is unclear. We have recently reported that induction of apoptosis of Mycobacterium bovis BCG-infected macrophages with ATP4- was associated with killing of the intracellular mycobacteria. In the present study, a long-term culture of M. avium-M. intracellulare-infected monocytes was used to further evaluate the interaction between M. avium-M. intracellulare and primary human monocytes. In our system, M. avium-M. intracellulare parasitized the human monocytes and appeared to replicate slowly over 14 days within the host cells. To examine the role of apoptotic mechanisms in survival or death of intracellular mycobacteria, M. avium-M. intracellulare-infected human monocytes were treated with a monoclonal antibody to Fas receptor (APO-1/CD95) or with various concentrations of H2O2. Although both of these exogenous agents induced monocyte apoptosis, optimal killing (65% reduction in CFU) of intracellular M. avium-M. intracellulare was observed only when M. avium-M. intracellulare-infected cells were treated with 10 mM H2O2. Fas-induced apoptosis did not affect M. avium-M. intracellulare viability. Our results suggest that not all stimuli of monocyte apoptosis induce killing of intracellular M. avium-M. intracellulare. Since release of H2O2 following phagocytosis of mycobacteria has been documented, H2O2-induced apoptotic death of M. avium-M. intracellulare-infected monocytes and its association with killing of the intracellular bacilli may be a physiological mechanism of host defense against M. avium-M. intracellulare.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Encapsulation of VIP into liposomes restores vasorelaxation in hypertension in situ.

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP) elicits vasodilation in the in situ peripheral microcirculation of hamsters with spontaneous hypertension and whether encapsulation of VIP into liposomes modulates this response. Using intravital microscopy, we found that suffusion of VIP (0.05 and 0.1 nmol) alone over cheek pouch resistance arterioles of normotensive hamsters elicited significant vasodilation that was potentiated and prolonged by encapsulation of the peptide into liposomes (P < 0.05). By contrast, VIP (0.5 and 0.1 nmol) had no significant effects on arteriolar diameter in hamsters with spontaneous hypertension. However, encapsulation of VIP into liposomes restored its vasorelaxant effects in hypertensive animals, although the duration of vasodilation was significantly shorter in comparison with controls (P < 0.05). Empty liposomes had no significant effects on arteriolar diameter in either group. These data indicate that VIP-induced vasodilation in the peripheral microcirculation in situ is impaired in essential hypertension and that encapsulation of VIP into liposomes restores, in part, this response.

Acetylcholine↗