Search PubMed⌕ Search

Biomedical subjects

J Tremblay

Publications and source records attributed to J Tremblay.

At least 55 records · Page 3Linked to original sources
PubMed1999

Sibling resemblance of erythrocyte ion transporters in French-Canadian sibling-pairs affected with essential hypertension.

OBJECTIVES: Erythrocyte Na+/Li+ countertransport and Na+,K+ cotransport are increased in some Caucasians with essential hypertension. This study examines the relative contributions of genetic and shared environmental factors to the activity of these ion carriers in French-Canadian sibling-pairs affected with essential hypertension. DESIGN: The activity of Na+/Li+ countertransport and Na+,K+ cotransport (rate of Na+ o-dependent Li+ efflux and bumetanide-sensitive 86Rb influx, respectively) was measured in 122 French-Canadian siblings with essential hypertension, including 36 brother/brother and 48 sister/sister pairs. Sibling/sibling correlations were estimated using the FCOR program of the S.A.G.E. package. RESULTS: Na+/Li+ countertransport and Na+,K+ cotransport were respectively higher by 27% (P = 0.002) and 42% (P = 0.0009) in erythrocytes from men compared with women. Intra-individual correlation analysis did not reveal a significant effect of age on the activity of these ion transporters in both males and females, and an influence of plasma lipids (triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein) in females. In males, Na+,K+ cotransport was correlated with the level of serum triglycerides only (P = 0.01). Familial correlation analysis showed that sibling resemblance of Na+/Li+ countertransport and Na+,K+ cotransport was higher in men (r = 0.26 and 0.39) than in women (r = 0.01 and 0.03, respectively). CONCLUSION: The present data indicate that different factors contribute to the regulation of monovalent ion carriers in erythrocytes from Caucasian men and women with essential hypertension. The activity of erythrocyte Na+/Li+ countertransport and Na+,K+ cotransport appears to be more strongly determined by inheritable factors in men than in women.

Adult↗
PubMed1999

Daily primary school physical education: effects on physical activity during adult life.

PURPOSE: The purpose of this investigation was to study the influence of a daily primary school physical education program on physical activity (PA) level, attitudes toward physical activity, and perceptions of barriers to physical activity during adulthood. METHODS: We compared two groups: 1) an experimental group of men and women (N = 147) who had received five physical education sessions per week throughout their 6 yr of primary school education in the early 1970s; and 2) a control group, drawn from the data bank of the Québec Health Survey, and matched for age, gender, and socioeconomic profile (N = 720). Experimental and control subjects filled out an identical questionnaire about their current physical activity level, their attitudes toward PA, and their perceptions of barriers to PA. The control group was stratified to obtain the same sociodemographic profile as the experimental group. RESULTS: Our principal results were: 1) a frequency distribution that showed a higher rate of physical activity in experimental women than in control women; 2) similar intentions to exercise and attitudes toward exercise in the experimental and control groups, with no differences in opportunities for exercising or in the support received from their family and friends; and 3) a lower prevalence of regular smokers in experimental men than in control men. There were also some differences in the types and frequency of physical activities selected between experimental and control subjects. CONCLUSION: Our results strongly suggest that daily physical education at the primary school level has had a significant long-term positive effect on the exercise habits on women, despite similar perceived barriers, attitudes, and intention to exercise in the two groups. The program has also had a significant health effect in men, substantially reducing the risk of becoming a regular smoker. Because the program was not specifically designed to promote health, we hypothesize that a health-oriented physical education program could have an even stronger effect.

Adult↗
PubMed1999

Protection against necrosis but not apoptosis by heat-stress proteins in vascular smooth muscle cells: evidence for distinct modes of cell death.

We have reported previously that cultured vascular smooth muscle cells (VSMC) isolated from spontaneously hypertensive rats (SHR) show higher proliferation and cell death than normotensive controls. In addition to protecting cells against death, heat stress proteins (HSPs) appear to play a role in cell proliferation. This investigation examines the involvement of HSP72 and HSP27 in altered SHR VSMC proliferation and death. We have performed detailed discriminatory analysis to characterize which type of VSMC death is induced by heat stress (HS) and serum deprivation. Serum deprivation induced apoptosis (caspase-3 cleavage and DNA laddering) and secondary necrosis, the 2 processes being a continuum of each other. In contrast, acute HS (46 degrees C, 30 minutes), which inhibited BN. lx and SHR VSMC proliferation by 2-fold, increased necrosis (by 5-fold and 2-fold, respectively) but not apoptosis. HSP72 and HSP27 expression evoked in VSMC by mild HS (44 degrees C, 15 minutes) 6 hours before acute HS prevented the inhibition of proliferation and induction of necrosis with no effect on serum deprivation-induced or staurosporine-induced apoptosis. This induced expression of HSP72 and HSP27 did not eliminate the higher basal proliferation, apoptosis, and necrosis of SHR VSMC compared with BN.lx VSMC, suggesting that these HSPs are not involved in altered SHR VSMC proliferation and death. Also, although apoptosis and necrosis may be a continuum, in VSMC the 2 processes may be distinguished by HS, in which only necrosis is prevented by prior HSP accumulation. This observation may be of use in designing strategies for cellular protection.

Animals↗
PubMed1999

Asynchronous development of bilateral nodular adrenal hyperplasia in gastric inhibitory polypeptide-dependent cushing's syndrome.

Gastric inhibitory polypeptide (GIP)-dependent Cushing's syndrome has been reported to occur either in unilateral adrenal adenoma or in bilateral macronodular adrenal hyperplasia. A 33-yr-old woman with Cushing's syndrome was found to have two 2.5- to 3-cm nodules in the right adrenal on computed tomography scan; the left adrenal appeared normal except for the presence of a small 0.8 x 0.6-cm nodule. Uptake of iodocholesterol was limited to the right adrenal. Plasma morning cortisol was 279 nmol/L fasting and 991 nmol/L postprandially, and ACTH remained suppressed. Plasma cortisol increased after oral glucose (202%) or a lipid-rich meal (183%), but not after a protein-rich meal (95%) or iv glucose (93%); the response to oral glucose was blunted by pretreatment with 100 microg octreotide, sc. Plasma cortisol and GIP levels were positively correlated (r = 0.95; P = 0.0001); cortisol was stimulated by the administration of human GIP iv (225%), but not by GLP-1, insulin, TRH, GnRH, glucagon, arginine vasopressin, upright posture, or cisapride orally. A right adrenalectomy was performed; GIP receptor messenger ribonucleic acid was overexpressed in both adrenal nodules and in the adjacent cortex. Histopathology revealed diffuse macronodular adrenal hyperplasia without internodular atrophy. Three months after surgery, fasting plasma ACTH and cortisol were suppressed, but cortisol increased 3.6-fold after oral glucose, whereas ACTH remained suppressed; this was inhibited by octreotide pretreatment, suggesting that cortisol secretion by the left adrenal is also GIP dependent. We conclude that GIP-dependent nodular hyperplasia can progress in an asynchronous manner and that GIPR overexpression is an early event in this syndrome.

Adrenal Glands↗
PubMed1999

Endotoxin response in spontaneously hypertensive rats: a role of the TNFalpha-gene region.

We have shown previously that administration of endotoxin induces a smaller decrease of body temperature in spontaneously hypertensive rats (SHR) than in normotensive Brown Norway (BN) rats. Several studies have suggested that tumor necrosis factor alpha (TNFalpha) is one of the mediators of the body-temperature response to endotoxin. To test whether the TNFalpha gene could be involved in determination of the observed difference in the body-temperature response to endotoxin, we studied SHR (n = 6) and a congenic strain, SHR.1N (n = 5), which differs from SHR by a segment of chromosome 20 originating from BN and containing the TNFalpha gene. Body temperature was recorded continuously by means of radiotelemetry. We showed that, in both strains, an intraperitoneal injection of endotoxin (500 microg/kg of body weight) induces a rapid hyperthermic phase (20-40 minutes post-injection), which is followed, first, by a hypothermic phase (100-120 minutes post-injection) and, then, by a late hyperthermic phase (seven hours). Although both strains demonstrated a similar trend in the response, a significant difference was observed between the two response curves (P = 0.0001). Further analysis at each time point revealed that the two strains differed significantly at a peak of the hypothermic phase (P = 0.035) and the late hyperthermic phase (P = 0.035). In conclusion, these data indicate that the differential chromosomal segment of SHR.1N contains a gene(s) causally related to the body-temperature response to endotoxin. In the light of previously published data, the TNFalpha gene appears to be the most likely candidate gene within the segment.

Animals↗
PubMed1998

Complete inhibition of Na+, K+, Cl- cotransport in Madin-Darby canine kidney cells by PMA-sensitive protein kinase.

This study examines the involvement of hormones and neuromediators in the regulation of Na+, K+, Cl- cotransport in renal epithelial cells using Madin-Darby canine kidney cells with low transepithelial electrical resistance (194+/-47 Omega/cm2). In this cell line, Na+, K+, Cl- cotransport measured as bumetanide-sensitive 86Rb influx was inhibited up to 50-60% with agonists of P2-purinoceptors (ATP approximately ADP>UTP>AMP), slightly (15-30%) increased by activators of cAMP signaling (forskolin, 8-Br-cAMP) and was insensitive to activators of cGMP signaling (8-Br-cGMP, nitroprusside), EGF, angiotensin II, bradykinin, methacholine, propranolol, vasopressin, adenosine, dopamine and histamine. Thirty min of preincubation of MDCK cells with 0.1 microM PMA completely blocked the activity of Na+, K+, Cl- cotransport whereas down-regulation of this enzyme by 24 h of preincubation with 1 microM PMA activated Na+, K+, Cl- cotransport by 60% and abolished the effect of short-term treatment with PMA. Regulation of Na+, K+, Cl- cotransport by ATP was insensitive to down-regulation of PMA-sensitive isoforms of protein kinase C. In addition, an inhibitor of protein kinase activity, staurosporine, abolished the effect of 0.1 microM PMA but did not change inhibition of this carrier by ATP. Thus, these results show for the first time that P2-purinoceptors and PMA-sensitive isoforms of protein kinase C play a key role in the regulation of Na+, K+, Cl- cotransport in MDCK cells. These results also show that neither PMA- nor staurosporine-sensitive forms of protein kinase are involved in the inhibition of Na+, K+, Cl- cotransport by activators of P2-purinoceptors.

Animals↗
PubMed1998

Molecular diversity and relationship within Lactococcus lactis, as revealed by randomly amplified polymorphic DNA (RAPD).

Lactococcus lactis strains are widely used in industrial dairy fermentations. Conventional phenotypic tests have been used for years to classify members of this species into two subspecies, lactis and cremoris, and play a key role in the choice of strains to be used in particular cheese fermentations. DNA hybridisation techniques have also been used for strain classification, giving rise to two genome homology groups. However, results showed discrepancies between the two methods of classification. We applied the randomly amplified polymorphic DNA fingerprinting (RAPD) technique to resolve previous contradictions in lactococcal classifications. Unlike usual RAPD methods, we use three primers to classify 113 strains and integrate the resulting information by a digitised programme used for this purpose. Our analysis revealed three major RAPD groups, designated G1, G2 and G3. G1 and G3 contain strains of the lactis subspecies, and G2 contains strains of the cremoris subspecies, as previously defined by phenotypic characteristics. Moreover, group G1 corresponds to one genome homology group, and groups G2 and G3 correspond to the second one. The taxonomic structure within L. lactis is therefore unusual: two distinct genetic groups of strains show indistinguishable phenotypes, while conversely, two phenotypically distinct groups are genetically homologous. We hypothesize that a subfamily of the subsp. lactis group gave rise to the cremoris subspecies.

DNA Fingerprinting↗
PubMed1998

Can we use erythrocytes for the study of the activity of the ubiquitous Na+/H+ exchanger (NHE-1) in essential hypertension?

Both Na+/Li+ countertransport and electrochemical proton gradient (delta mu(H+))-induced Na+ and H+ fluxes are increased in erythrocytes from patients with essential hypertension. It was assumed that these abnormalities are related to ubiquitous (housekeeping) forms of the Na+/H+ exchanger (NHE-1). To examine this hypothesis, we compared kinetic and regulatory properties of erythrocyte Na+/Li+ countertransport and delta mu(H+)-induced Na+ and H+ fluxes with data obtained for cloned isoforms of the Na+/H+ exchanger. In human erythrocytes, Na+/Li+ countertransport exhibited a hyperbolic dependence on [Na+]0 with a K0.5 of approximately 30 to 40 mmol/L. The activity of this carrier was increased by two-fold in the fraction of erythrocytes enriched with the old cells, was inhibited by 0.1 mmol/L phloretin, and was insensitive to both 1 mmol/L amiloride and ATP depletion. In contrast, delta mu(H+)-induced 22Na influx was exponentially increased at [Na+]0 > 60 mmol/L, was insensitive to phloretin, was partly decreased by both 1 mmol/L amiloride and ATP depletion, and was the same in total erythrocytes and in the old cells. The values of Na+/Li+ countertransport and delta mu(H+)-induced Na+ influx in erythrocytes from different species were not correlating and their ratio in human, rat, and rabbit erythrocytes was 10:1:170 and 1:5:1 for Na+/ Li+ countertransport and delta mu(H+)-induced Na+ influx, respectively. In contrast to the majority of nonepithelial cells and cells transfected with an ubiquitous isoform of Na+/H+ exchanger, both delta mu(H+)-induced Na+ influx and Na+/Li+ countertransport in human erythrocytes were completely insensitive to ethylisopropyl amiloride (20 micromol/L) and cell shrinkage. Thus, our data strongly suggest that human erythrocyte Na+/Li+ countertransport and delta mu(H+)-induced Na+/H+ exchange are mediated by the distinct transporters. Moreover, because the properties of these erythrocyte transporters and NHE-1 are different, it complicates the use of erythrocytes for the identification of the mechanism for activating the ubiquitous form of Na+/H+ exchanger in primary hypertension.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Newborn and adult recombinant inbred strains: a tool to search for genetic determinants of target organ damage in hypertension.

It has been proposed that one of the primary events in the development of essential hypertension is a growth-related process initiated as early as during fetal development. Differences in kidney size have been observed between most rat models of hypertension and their respective controls. In this study, we analyzed relative kidney size (kidney weight/body wt) in a set of rat recombinant inbred strains (RIS) (N = 27) and their progenitors, the spontaneously hypertensive rat strain (SHR/Ola) and Brown Norway congenic strain (BN.1x), at two different ages, at birth and at 15 weeks. In the progenitors, the relative kidney weight was higher in the hypertensive than in the normotensive strain of both the newborn (P < 0.001) and adult (P < 0.001) animals. In the RIS, a significant correlation was found between the newborn and adult relative kidney weight (r = 0.49, P = 0.01), indicating that the two phenotypes share some of their genetic determinants. A total genome search of newborn and adult relative kidney weight was performed with a total of 453 genetic markers. These analyses revealed several suggestive quantitative trait loci (QTL), some of which were, indeed, significant for both newborn and adult relative kidney weight (such as, D3Mit9 on rat chromosome 3; r = -0.50, P < 0.01; r = -0.47, P < 0.01; respectively). Others, such as the locus on rat chromosome 1 (Rt6; r = -0.43, P < 0.05), were significant only for the adult relative kidney size. This QTL was found in close proximity to a region previously related to susceptibility to hypertensive renal disease in the fawn-hooded rat and, similarly to that study, its effect was found to be independent of blood pressure. Furthermore, a growth pattern of the kidneys after birth, evaluated as the difference between the newborn and adult relative kidney weight, was also subjected to total genome scan. Several suggestive QTL were identified. One of the most significant loci was found at the D1a marker on rat chromosome 17 (r = -0.51, P < 0.01), which was previously related to the determination of adult heart weight in the RIS. In conclusion, the current study demonstrates the usefulness of RIS in studies of hypertension-related phenotypes, some of which are abnormal before the development of high blood pressure. To better understand their role in the pathogenesis of hypertension, studies at different ages are needed, which are uniquely feasible in RIS.

Aging↗
PubMed1998

Hypertension: genes and environment.

Hypertension can be classified as either Mendelian hypertension or essential hypertension, on the basis of the mode of inheritance. The Mendelian forms of hypertension develop as a result of a single gene defect, and as such are inherited in a simple Mendelian manner. In contrast, essential hypertension occurs as a consequence of a complex interplay of a number of genetic alterations and environmental factors, and therefore does not follow a clear pattern of inheritance, but exhibits familial aggregation of cases. In this review, we discuss recent advances in understanding the pathogenesis of both types of hypertension. We review the causal gene defects identified in several monogenic forms of hypertension, and we discuss their possible relevance to the development of essential hypertension. We describe the current approaches to identifying the genetic determinants of human essential hypertension and rat genetic models of hypertension, and summarise the results obtained to date using these methods. Finally, we discuss the significance of environmental factors, such as stress and diet, in the pathogenesis of hypertension, and we describe their interactions with specific hypertension susceptibility genes.

Animals↗
PubMed1998

Estimation of the state of the bacterial cell wall by fluorescent In situ hybridization.

Fluorescent in situ hybridization (FISH) is now a widely used method for identification of bacteria at the single-cell level. With gram-positive bacteria, the thick peptidoglycan layer of a cell wall presents a barrier for entry of horseradish peroxidase (HRP)-labeled probes. Therefore, such probes do not give any signal in FISH unless cells are first treated with enzymes which hydrolyze the peptidoglycan. We explored this feature of FISH to detect cells which have undergone permeabilization due to expression of autolytic enzymes. Our results indicate that FISH performed with HRP-labeled probes provides a sensitive method to estimate the states of cell walls of individual gram-positive bacteria.

Amidohydrolases↗
PubMed1998

Na+/H+ exchange in vascular smooth muscle cells is controlled by GTP-binding proteins.

This study examines the involvement of GTP-binding proteins (Gps) in the regulation of Na+/H+ exchange and Ca2+ influx, which are increased in vascular smooth muscle cells from spontaneously hypertensive rats. Gp activity was modulated by fluoride, GTPgammaS, GDPbetaS, and antisense oligodeoxynucleotides complementary to conserved regions of the alpha- and beta-subunits of Gps (alpha-comm and beta-comm, respectively). Beta-adrenergic-induced Gs-mediated cAMP production was used as a positive control to estimate the efficiency of these compounds. Na+/H+ exchange, measured as ethylisopropyl amiloride-sensitive 22Na influx, was activated by 5- to 6-fold by a 30-minute preincubation of cells with 10 mmol/L NaF with a K0.5 for NaF of approximately 13 mmol/L. In contrast, no activation of 45Ca influx was observed under preincubation of vascular smooth muscle cells with NaF in Ca2+-free medium, whereas at [Ca2+]o >0.5 mmol/L, simultaneous addition of 45Ca and 10 mmol/L NaF led to sharply increased isotope uptake. NaF-induced 45Ca influx did not reach saturation up to 3 mmol/L [Ca2+]o and 20 mmol/L NaF and was correlated with the formation of calcium-fluoride complexes measured by light scattering. GTPgammaS increased basal cAMP production and Na+/H+ exchange, whereas GDPbetaS decreased isoproterenol-induced cAMP production and Na+/H+ exchange. Alpha-comm reduced whereas beta-comm augmented isoproterenol-induced cAMP production by 70%. Both oligodeoxynucleotides decreased basal Na+/H+ exchange by 40% to 50%. NaF-induced Na+/H+ exchange was not sensitive to alpha-comm but was inhibited by 60% in beta-comm-loaded cells. Neither basal nor NaF-induced 45Ca uptake was affected by GTPgammaS, GDPbetaS, and the oligodeoxynucleotides. Our results show that 45Ca uptake is activated by NaF in vascular smooth muscle cells by nonspecific accumulation of calcium-fluoride complexes and is not related to modification of Gps. On the contrary, the Na+/H+ exchanger is controlled by Gps, and Gp beta-subunits are involved in [Ca2+]o-independent activation of this carrier by NaF.

Aluminum Chloride↗
PubMed1998

Adrenocortical overexpression of gastric inhibitory polypeptide receptor underlies food-dependent Cushing's syndrome.

Abnormal responsiveness of adrenocortical cells to gastric inhibitory polypeptide (GIP) in food-dependent Cushing's syndrome suggested that adrenal expression of ectopic, overexpressed, or mutated GIP receptor (GIPR) underlies this syndrome. The expression of GIPR was studied by RT-PCR in human adrenal tissues from two patients with GIP-dependent Cushing's syndrome (adenoma, bilateral hyperplasia), five fetal or adult controls, one patient with Cushing's disease, and four patients with non-food-dependent cortisol-secreting adenomas or bilateral hyperplasias and compared to that in normal pancreas. Hybridization of the RT-PCR-amplified ribonucleic acids with the human GIPR complementary DNA showed an overexpression of GIPR in the adrenals of the two GIP-dependent Cushing's syndrome patients compared to that in normal adrenal tissues (2-3 orders of magnitude) or pancreas (10-fold); no signal could be seen in adrenal adenomas or macronodular hyperplasia from cases of non-food-dependent Cushing's syndrome. No mutation of the GIPR was identified by sequencing the full-length receptor in GIP-dependent adrenal tissue. New alternative spliced isoforms of the GIPR were found, but are identical in GIP-dependent and normal adrenal tissues. Incubation of adrenal cells with GIP stimulates cortisol secretion in GIP-dependent, but not in normal fetal, adult, or non-food-dependent Cushing's syndrome, adrenals. We conclude that the GIPR overexpression and its coupling to steroidogenesis underlie GIP-dependent Cushing's syndrome.

Adrenal Cortex↗
PubMed1998

Decision support for medication use in an inpatient physician order entry application and a pharmacy application.

Studies have shown that adverse drug events are common, expensive, and due to causes that can be remedied by information technologies. At our institution we have developed a physician order entry application and a pharmacy application designed to decrease the risk of such adverse drug events. In this paper, we describe the applications, with attention to the clinical decision support features present in each. We also describe the manner in which the two applications interact.

Clinical Pharmacy Information Systems↗
PubMed1997

Increase in the proliferative capacity of human myoblasts by using the T antigen under the vimentin promoter control.

Normal myoblasts have a strictly limited growth potential and senesce after a defined number of population doubling. The objective of this study was to determine whether the proliferative capacity of human myoblasts could be extended without inhibiting myogenic differentiation. We have established a stable transfected human myoblast cell line that expresses the SV 40 large T antigen under the control of the human vimentin promoter. We show that these cells have an increased proliferative capacity compared with that of normal myoblasts. Indeed, the final proliferative capacity was increased to 19 passages (5 for normal myoblasts). Moreover, they retained their capacity to differentiate fully, as indicated by their morphology and electrophysiological properties as well as by the expression of different markers of differentiation. The generation of human myogenic cell lines with the ability to proliferate for a longer period of time than primary myoblasts and while retaining the capacity to differentiate into myotubes could provide a valuable tool for the derivation of cell lines from human diseased muscle cells.

Antigens, Viral, Tumor↗
PubMed1997

Positive chronotropic and inotropic effects of C-type natriuretic peptide in dogs.

We have recently reported that C-type natriuretic peptide (CNP) has a positive chronotropic effect in dogs. We further investigated the effect of CNP on canine cardiac functions: 1) in situ, by exploring the effects of isoproterenol (10 microg), angiotensin II (ANG II, 5 microg), and CNP (40 microg) injections (n = 8) on computerized epicardial mapping of atrial activation to detect a shift in pacemaker location; 2) by examining the presence of natriuretic peptide receptor (NPR)-A and -B mRNAs in atrial and nodal tissues using semiquantitative reverse-transcription polymerase chain reaction; 3) in vitro, using spontaneously beating right atrial preparations (n = 6), by recording the transmembrane potentials of sinoatrial node (SAN) cells before and after injection of CNP (25 microg); and 4) by observing the effects of CNP (25 microg) on contractile force of paced isolated right atrial preparations (n = 6). The results indicate that 1) the site of earliest extracellular electrical activation in the SAN remains mostly unchanged in response to CNP, whereas it shifts to the superior region of the SAN after isoproterenol and ANG II injections; 2) NPR-A and -B mRNAs are present in atrial and nodal tissues; 3) CNP significantly increases the maximal rate of diastolic depolarization and decreases the action potential duration at 75 and 90% of repolarization; and 4) CNP significantly increases atrial contractile force. These results suggest that CNP modifies cardiac ionic currents to produce positive chronotropic and inotropic effects by stimulation of NPR-B receptors, located in the SAN region, and that CNP plays a role in the modulation of cardiac function.

Action Potentials↗
PubMed1997

The antiadhesive and antithrombotic effects of the nitric oxide donor SIN-1 are combined with a decreased vasoconstriction in a porcine model of balloon angioplasty.

Nitric oxide has been reported to modulate platelet and neutrophil interactions with the arterial wall. In this study, we investigated the effects of the nitric oxide donor 3-morpholino-sydnonimine (SIN-1) on platelet and neutrophil adhesion, and the vasomotor response, in a porcine model of angioplasty. Carotid arterial injury was produced by balloon dilation in control (n = 10) and treated (SIN-1; 10 micrograms/kg + 1 microgram/kg/min, i.v.) (n = 8) pigs. At the site of deep arterial injury, the average platelet adhesion was 53.6 +/- 11.3 x 10(6)/cm2 in the control animals and was significantly inhibited by more than 70%, to 15.1 +/- 4.1 x 10(6)/cm2 (P < .01), by SIN-1. Neutrophil adhesion was also decreased by SIN-1, from 255.9 +/- 29.7 to 101.8 +/- 19.7 x 10(3)cm2 (P < .001). Mural thrombosis was found in 12 (71%) of the 17 injured arteries in the control group but in only 2 (17%) of the 12 injured arteries in the SIN-1-treated group (P < .05). Concomitantly, SIN-1 reduced platelet and neutrophil adhesion to the site of endothelial injury distally. The internal diameter of the carotid arteries was similar between the two groups before dilation but was 40% greater at the site of endothelial injury distally in SIN-1-treated animals after dilation (P < .05), as compared with controls. Accordingly, postangioplasty vasoconstriction was significantly attenuated from 46.3 +/- 2.9% in control pigs to 32.5 +/- 4.8% (P < .05) in SIN-1-treated animals. The beneficial effects of SIN-1 were associated with inhibition of neutrophil-mediated whole blood aggregation and of neutrophil-endothelium interactions. The potent antiadhesive and antithrombotic properties of SIN-1 in vivo were confirmed in ex vivo superfusion experiments. These results indicate that administration of a nitric oxide donor may be effective in preventing the acute pathophysiological responses to arterial injury by angioplasty.

Angioplasty, Balloon↗