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S J Hutchison

Publications and source records attributed to S J Hutchison.

At least 19 recordsLinked to original sources
PubMed1999

Coronary vasodilator effects of BNP: mechanisms of action in coronary conductance and resistance arteries.

Brain natriuretic peptide (BNP), a hormone secreted predominantly in ventricular myocytes, may influence coronary vascular tone. We studied the coronary vasodilatory response to BNP under physiological conditions and after preconstriction with endothelin-1 (ET-1) in anesthetized pigs. Average peak-flow velocity (APV) was measured using intracoronary Doppler, and cross-sectional area (CSA) was measured using intravascular ultrasound. Coronary blood flow (CBF) was calculated. Intracoronary BNP induced dose-dependent increases in CSA, APV, and CBF similar in magnitude to those induced by nitroglycerin (NTG). The magnitude of BNP-induced vasodilation was accentuated after preconstriction with ET-1. Pretreatment with either the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester or the cyclooxygenase inhibitor indomethacin attenuated the coronary vasodilator effect of BNP in resistance arteries without influencing epicardial vasodilation. Pretreatment with the ATP-sensitive potassium-channel blocker glibenclamide enhanced epicardial vasodilation in response to BNP. We conclude that BNP exerts coronary vasodilator effects, predominantly in epicardial conductance vessels. An accentuated vasodilatory response to BNP occurs in ET-1-preconstricted arteries. BNP-induced vasodilation in coronary resistance arteries may be partially mediated via nitric oxide and/or prostaglandin release.

Animals↗
PubMed1999

Effects of L-arginine on atherogenesis and endothelial dysfunction due to secondhand smoke.

Secondhand smoke (SHS) and hypercholesterolemia increase cardiovascular risk. We hypothesized that L-arginine, the precursor of nitric oxide (NO), might protect against atherogenesis and endothelial dysfunction caused by SHS. The effects of L-arginine supplementation (2.25% solution ad libitum) and SHS (smoking chambers for 10 weeks) were examined in 32 hypercholesterolemic rabbits. Eight normal rabbits served as controls. Acetylcholine- and nitroglycerin-induced vasorelaxation was assessed in aortic rings precontracted with norepinephrine. Hypercholesterolemia increased intimal lesion area (P=0.012), reduced endothelium-dependent relaxation (P=0.009), and reduced basal (P=0.005) and stimulated (P<0.0005) production of NOs. SHS increased intimal lesion area (P=0. 01) norepinephrine-induced contraction (P=0.001) and reduced endothelium-dependent relaxation (P=0.02). SHS-induced increase in norepinephrine contraction was abolished by the inhibition of NO synthase and removal of endothelium. L-Arginine improved endothelium-dependent relaxation (P=0.001) and attenuated SHS-induced endothelial dysfunction (P=0.007) and atherogenesis (P=0. 001). Basal production of nitrogen oxides correlated inversely with intimal lesion area (r=-0.66; P<0.0005) and stimulated production of NOs correlated with endothelium-dependent relaxation (r=-0.66; P<0. 001). SHS causes endothelial dysfunction and increased adrenergic responsiveness and atherogenesis in hypercholesterolemic rabbits. Chronic dietary supplementation with the NO precursor L-arginine mitigates these effects. The adverse vascular consequences of SHS appear to be mediated via deleterious effects on endothelial function.

Animals↗
PubMed1998

In-utero and neonatal exposure to secondhand smoke causes vascular dysfunction in newborn rats.

OBJECTIVES: We sought to determine the effects of secondhand smoke (SHS) exposure on vascular reactivity in newborn and infant rats. BACKGROUND: Secondhand smoke exposure increases cardiovascular risk. Secondhand smoke-induced endothelial dysfunction has been demonstrated in older teenagers and young adults. We have previously shown in adult rabbits that SHS induces atherogenesis and endothelial dysfunction. The effects of SHS on vascular function in the offspring of SHS-exposed mothers and in infants are unknown. METHODS: In this study the effects of in-utero (21 days) and neonatal (28 days) exposure to SHS were examined in 80 rats, 4 weeks of age, in a 2-by-2 design study. Rats were exposed to sidestream smoke in smoking chambers. Aortic rings were excised and isometric force responses to phenylephrine, acetylcholine, A23187 and nitroglycerin were studied in organ baths. RESULTS: Neonatal SHS exposure reduced animal weight (p=0.009). In-utero exposure increased the sensitivity (decreased the EC50) of aortic rings to phenylephrine (p < 0.0005), as did neonatal exposure (p=0.01). Maximal contraction to phenylephrine was reduced by in-utero exposure (p=0.04). In-utero SHS exposure reduced maximal endothelium-dependent relaxation to acetylcholine (p=0.04) and increased the EC50 (p=0.05), suggesting impaired sensitivity to acetylcholine. In-utero exposure decreased the sensitivity (increased the EC50) to the endothelium-independent vasodilator nitroglycerin (p=0.003). CONCLUSIONS: Secondhand smoke has detrimental effects on vascular smooth muscle function in the newborn.

Acetylcholine↗
PubMed1997

Physiological concentrations of estradiol attenuate endothelin 1-induced coronary vasoconstriction in vivo.

BACKGROUND: Estrogens are cardioprotective hormones and are reported to have antianginal properties. We examined the effect of physiological concentrations of 17beta-estradiol on coronary reactivity in anesthetized female farm pigs. METHODS AND RESULTS: Epicardial coronary cross-sectional area (CSA) was assessed by two-dimensional intravascular ultrasound, average coronary peak flow velocity (APV) by intravascular Doppler velocimetry, and coronary blood flow (CBF) was calculated. Dose-response curves to intracoronary endothelin-1 (ET-1, 1 pmol/L to 10 nmol/L), the selective ET(B) receptor agonist sarafotoxin (1 pmol/L to 10 nmol/L), and serotonin (0.1 nmol/L to 1 micromol/L) were assessed before and after a 10-minute infusion of intracoronary estradiol (1 nmol/L). Before estradiol administration, ET-1 induced significant dose-dependent decreases in CSA, APV, and CBF. Estradiol attenuated ET-1-induced epicardial vasoconstriction (P<.001) as well as ET-1-induced decreases in APV (P=.05) and CBF (P=.012). In an additional five pigs, vehicle (DMSO) had no effect on ET-1-induced coronary vasoconstriction. Before estradiol administration, sarafotoxin induced no net change in CSA but induced increases in APV and CBF, the extent of which did not change significantly after estradiol. Serotonin induced small decreases in CSA but increased APV and CBF. Estradiol did not influence serotonin-induced changes in CSA, APV, or CBF. CONCLUSIONS: We conclude that estradiol attenuates ET-1-induced vasoconstriction, possibly through effects on the ET(A) receptor, because selective ET(B) receptor-induced stimulation with sarafotoxin remained unchanged. Such an effect on the ET(A) receptor may relate to the antianginal properties of estrogens.

Animals↗
PubMed1997

Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta.

OBJECTIVES: To assess the effects of interaction of sex hormones, hypercholesterolemia (HC) and environmental tobacco smoke (ETS) exposure on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of atherogenesis. BACKGROUND: Animal and human studies indicate the presence of interactions between classic coronary artery disease risk factors and endothelium-dependent relaxation. Sex hormones have also been shown to influence release of endothelium-derived relaxing factor. METHODS: New Zealand White rabbits were randomized to receive either an HC diet (n = 8) or ETS exposure plus HC diet (n = 8). Eight rabbits receiving a normal diet, without exposure to ETS, served as the control group. The HC diet consisted of 3% soybean oil and 0.3% cholesterol by weight over 13 weeks. The source of ETS was sidestream smoke of 4 cigarettes/15 min, 6 h/day, 5 days/week over 10 weeks in a smoking chamber. Rabbits were killed, and fresh aortic rings were harvested and maintained in oxygenated Krebs solution in an organ bath at 37 degrees C. Rings were precontracted with norepinephrine and exposed to acetylcholine in increasing doses, and isometric tension was recorded. Rings were also exposed to physiologic concentrations (1 nmol/liter) of either 17-beta-estradiol, testosterone or progesterone before pre-contraction with norepinephrine and relaxation with acetylcholine. Endothelium-independent relaxation was studied using nitroglycerin. The surface area of the ring covered by lipids was measured by Sudan IV staining. RESULTS: HC and ETS significantly reduced endothelium-dependent relaxation (p = 0.01 and p < 0.0005, respectively) and caused atherogenesis (p < 0.0005 and p = 0.047, respectively) but did not affect endothelium-independent relaxation. Incubation with estradiol and estradiol plus progesterone did not influence endothelium-dependent relaxation. Testosterone reduced endothelium-dependent relaxation (p = 0.049) and augmented the endothelial dysfunction associated with ETS exposure and HC (p = 0.03). CONCLUSIONS: Both HC and ETS are atherogenic and impair endothelial function but do not affect endothelium-independent relaxation. Physiologic levels of estradiol and estradiol plus progesterone do not affect endothelium-dependent relaxation. Physiologic levels of testosterone impair relaxation and augment the endothelial dysfunction associated with ETS exposure and HC.

Animals↗
PubMed1997

Everest nails.

Explore the source record for details and available documents.

Adult↗
PubMed1997

Sex hormones and vascular reactivity.

It is increasingly recognized that sex steroids have, among many other effects, the ability to cause vasodilation. The vasodilatory effects of estradiol have been the best documented and described. At low concentrations, estradiol has the ability to improve impaired endothelium dependent (nitric oxide mediated) relaxation in estrogen deficient subjects. At high concentrations, estradiol causes vasodilation principally by endothelium independent mechanisms, in a gender independent fashion, which appear to involve a number of pathways such as ATP-dependent K+ channels. Testosterone also has ability, at higher doses, to cause vasodilation of the coronary circulation, in a gender independent fashion. The mechanisms of sex steroid-induced vasodilation are reviewed in this article.

Animals↗
PubMed1997

Determination of coronary flow measurements by transesophageal echocardiography: dependence of flow velocity reserve on the location of stenosis.

Doppler velocimetry with the use of transesophageal echocardiography can record flow in the proximal left anterior descending artery (LAD). To assess whether this limited sampling ability influences the recording of velocity and the calculation of coronary flow reserve (CFR), 32 patients with LAD stenosis (4 ostial stenoses, 18 proximal stenoses, 10 mid-LAD stenoses) and 33 patients with arteriographically normal LADs were studied. Basal flow and dipyridamole-induced hyperemic flow rates were recorded. The mean basal flow velocity in ostial stenoses was greater than in other groups, and the mean basal flow velocity in proximal stenoses was less than that in mid-LAD stenoses and in the normal group. Maximal hyperemic velocity did not differ between the groups. CFR in all stenoses groups was less than that in the normal group. Ostial CFR was less than in all other groups, and proximal CFR was less than that in either the mid-LAD or the normal LAD groups. With this technique, coronary flow velocimetry and estimation of CFR is affected by the location of stenosis.

Aged↗
PubMed1997

Effects of second-hand smoke and gender on infarct size of young rats exposed in utero and in the neonatal to adolescent period.

OBJECTIVES: We sought to assess the effects of second-hand smoke (SHS) and gender on infarct size in young rats exposed in utero or in the neonatal to adolescent period, or both. BACKGROUND: We previously demonstrated that exposure to SHS increases infarct size in a rat model of ischemia and reperfusion, with a dose-response relation. These results are consistent with epidemiologic studies demonstrating that SHS increases risk of death from heart disease. METHODS: Thirty-one pregnant female rats were randomly divided into two groups: those exposed to SHS and a control group (non-SHS). After 3 weeks, each rat had given birth to 10 to 12 rats. One hundred one neonatal rats were divided into four groups according to exposure to SHS in utero (SHSu) and randomized to SHS exposure in the neonatal to adolescent period (SHSna). After 12 weeks, all rats were subjected to 17 min of left coronary artery occlusion and 2 h of reperfusion. RESULTS: Birth mortality was higher in the SHSu group than in the non-SHSu group (11.9% vs. 2.8%, p < 0.001). Body weight of neonatal rats at 3 and 4 weeks in the two SHSu groups was lower than that of rats in the two non-SHSu groups (p < 0.001). Exposure to SHSna increased endothelin-1 levels in plasma (p = 0.001). In all 70 young rats who survived the neonatal period, infarct size (Infarct mass/Risk area x 100%) was greater in the SHSna groups than in the non-SHSna groups (p = 0.005) and in the male groups than in the female groups (p < 0.001). CONCLUSIONS: Exposure to SHS in the neonatal to adolescent period and male gender increased myocardial infarct size in a young rat model of ischemia and reperfusion. These results are consistent with epidemiologic studies demonstrating that SHS increases the health risk to neonates and adolescents.

Angiotensin II↗
PubMed1997

Chronic dietary L-arginine prevents endothelial dysfunction secondary to environmental tobacco smoke in normocholesterolemic rabbits.

Our goal was to determine whether environmental tobacco smoke causes endothelial dysfunction in the absence of hypercholesterolemia and whether such an effect can be prevented by supplementation with L-arginine. Environmental tobacco smoke exposure is associated with an increase in coronary artery disease events and mortality. We have previously demonstrated that environmental tobacco smoke causes endothelial dysfunction and atherosclerosis in rabbits with diet-induced hypercholesterolemia and atherosclerosis and that chronic dietary L-arginine supplementation prevents this. The effects of L-arginine supplementation (2.25% solution ad libitum) and environmental tobacco smoke (smoking chambers for 10 weeks) were examined with a 2 x 2 design in 32 rabbits fed a normal diet. Acetylcholine, calcium ionophore A23187, and nitroglycerin-induced vasorelaxation were assessed in aortic rings precontracted with phenylephrine. Endothelial L-arginine levels were measured by chromatography. Chronic L-arginine supplementation increased serum (P < .001) and endothelial (P = .003) L-arginine levels. Environmental tobacco smoke reduced endothelium-dependent acetylcholine-induced relaxation, and L-arginine blocked this adverse effect (P = .04). Environmental tobacco smoke tended to increase phenylephrine-induced contraction (P = .06). Neither environmental tobacco smoke nor L-arginine influenced A23187-induced relaxation nor endothelium-independent nitroglycerin-induced relaxation. Endothelial dysfunction secondary to environmental tobacco smoke may occur in the absence of diet-induced hypercholesterolemia and atherosclerosis. Chronic dietary supplementation with a nitric oxide donor such as L-arginine offsets the endothelial dysfunction associated with environmental tobacco smoke in normocholesterolemic rabbits, possibly through substrate loading of the nitric oxide pathway.

Animals↗
PubMed1996

Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo.

BACKGROUND: Although estrogens have been shown to be vasoactive hormones, the vascular effects of testosterone are not well defined. Like estrogen, testosterone causes relaxation of isolated rabbit coronary arterial segments. We examined the vasodilator effects of testosterone in vivo in the coronary circulation and the potential mechanisms of its actions. METHODS AND RESULTS: Using simultaneous intravascular two-dimensional and Doppler ultrasound, we examined the effect of intracoronary testosterone in coronary conductance and resistance arteries in 10 anesthetized dogs (5 male, 5 female). We also assessed the contribution of NO, prostaglandins, ATP-sensitive K+ channels, and classic estrogen receptors to testosterone-induced vasodilation. Testosterone induced a significant increase in cross-sectional area, average coronary peak flow velocity, and calculated volumetric coronary blood flow at the 0.1 and 1 mumol/L concentrations. This effect was independent of sex. Pretreatment with N omega-nitro-L-arginine methyl ester to block NO synthesis decreased testosterone-induced increase in cross-sectional area, average coronary peak flow velocity, and coronary blood flow. Pretreatment with glybenclamide to assess the role of ATP-sensitive K+ channels did not influence testosterone-induced dilation in epicardial arteries but did attenuate its effect in the microcirculation. Pretreatment with indomethacin or the classic estrogen-receptor antagonist ICI 182,780 did not alter testosterone-induced changes. CONCLUSIONS: Short-term administration of testosterone induces a sex-independent vasodilation in coronary conductance and resistance arteries in vivo. Acute testosterone-induced coronary vasodilation of epicardial and resistance vessels is mediated in part by endothelium-derived NO. ATP-sensitive K+ channels appear to play a role in the vasodilatory effect of testosterone in resistance arteries.

Animals↗
PubMed1996

Coronary vasodilation induced by angiotensin-converting enzyme inhibition in vivo: differential contribution of nitric oxide and bradykinin in conductance and resistance arteries.

BACKGROUND: We studied in coronary conductance and resistance arteries the coronary vasodilator effects of the angiotensin-converting enzyme inhibitor ramiprilat and the contribution of nitric oxide, bradykinin, and prostaglandins to this vasodilation. METHODS AND RESEARCH: In seven anesthetized dogs, a Doppler guidewire was placed in the circumflex coronary artery to measure coronary flow velocity, and an ultrasound imaging catheter was introduced over the Doppler wire to measure coronary cross-sectional area. Drugs were infused directly into the left main coronary artery to minimize systemic effects. Ramiprilat increased both epicardial cross-sectional area and coronary blood flow velocity, resulting in an increase in absolute coronary blood flow. Pretreatment with N omega-nitro-L-arginine methyl ester (100 micromol/L intracoronary) to block nitric oxide synthase attenuated ramiprilat-induced increase in epicardial coronary cross-sectional area (P<.05) but not in coronary flow velocity or coronary blood flow. In contrast, pretreatment with the selective bradykinin antagonist HOE 140 (10 micromol/L) attenuated ramiprilat-induced increase in flow velocity (P<.025) and coronary blood flow (P<.05) but not epicardial coronary cross-sectional area. Pretreatment with indomethacin (5 mg/kg body wt IV) did not alter ramiprilat-induced increase in epicardial cross-sectional area, nor did it significantly influence coronary blood flow. CONCLUSIONS: Other than decreasing angiotensin II production, acute ramiprilat-induced vasodilation in canine coronary conductance arteries is mediated in part by nitric oxide. Ramiprilat-induced vasodilation in resistance arteries is in part mediated by the action of bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Morphological characteristics of the regurgitant rheumatic mitral valve.

Reparative surgery for valvular insufficiency is attempted frequently. The success of surgery depends partly on the underlying etiology. To establish the morphological characteristics of rheumatic mitral valve disease (insufficiency) (n = 12), mitral insufficiency due to infective endocarditis (n = 12), mitral insufficiency postinfarction (n = 6), rheumatic (predominant) mitral insufficiency postinfarction (n = 6), rheumatic (predominant) mitral stenosis (n = 12) and normal patients (n = 12) were examined retrospectively. In the groups of patients with mitral insufficiency< the mobility of the posterior leaflet tip (change in angle from the annular plane) was significantly less than normal 48 +/- 9 degrees only in the rheumatic group (12 +/- 7 degrees, P < 0.01). The posterior mitral leaflet tip had greater than normal mobility in the other mitral insufficiency groups: infective endocarditis 53 +/- 15 degrees (P = 0.35 versus normals), postinfarction 63 +/- 11 degrees (P = 0.02 versus normals), myxomatous 63 +/- 19 degrees (P = 0.03 versus normals). The mobility of the posterior mitral leaflet tip was also significantly less than normal in the rheumatic mitral stenosis group: 16 +/- 7 degrees, P < 0.01 versus normals. In the two rheumatic groups, diastolic doming of the anterior mitral leaflet was seen solely in mitral stenosis. In the predominant regurgitant group, the tip of the anterior mitral leaflet was much more mobile than in the stenosis group. Doming of the anterior mitral leaflet was absent from the predominant regurgitant group (2.1 +/- 0.9 cm, P < 0.001). The stenotic mitral valves domed 0.75 +/- 0.15 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography, Doppler, Color↗