Biomedical subjects

A M Dart

Publications and source records attributed to A M Dart.

At least 73 records · Page 4Linked to original sources

PubMed1997

Ins(1,4,5)P3 and arrhythmogenic responses during myocardial reperfusion: evidence for receptor specificity.

Reperfusion of ischemic rat hearts initiates the generation of inositol(1,4,5)trisphosphate [Ins(1,4,5)P3] and arrhythmias, provided that either norepinephrine or thrombin is present. In the current study, effects on endothelin-1 (ET-1) responses were investigated. Reperfusion of catecholamine-depleted, [3H]inositol-labeled hearts in the presence of ET-1 caused an increase in [3H]inositol phosphates (7,073 +/- 1,004 to 17,300 +/- 206 counts.min-1.g tissue-1, means +/- SE, n = 4, P < 0.01), which was quantitatively greater than the release observed under normoxic conditions, but there was no increase in [3H]Ins(1,4,5)P3. Gentamicin (150 microM) inhibited inositol phosphate responses in the presence of either norepinephrine or thrombin but did not inhibit the response to ET-1, providing additional evidence that the inositol phosphate response to ET-1 does not involve formation of Ins(1,4,5)P3, even under reperfusion conditions. In contrast to norepinephrine and thrombin, ET-1 did not initiate reperfusion arrhythmias (4.4% ventricular fibrillation compared with 0% ventricular fibrillation in catecholamine-depleted controls). The data provide strong evidence that the effect of ischemia-reperfusion on inositol phosphate responses is specific for particular receptor types and eliminates G proteins, phospholipase C enzymes, and substrate availability as the primary factors responsible for Ins(1,4,5)P3 generation under reperfusion conditions.

Animals↗

PubMed1997

Arterial compliance increases after moderate-intensity cycling.

Exercise training elevates arterial compliance at rest, but the effects of acute exercise in this regard are unknown. This study investigated the effects of a single, 30-min bout of cycling exercise at 65% of maximal oxygen consumption on indexes of arterial compliance. Whole body arterial compliance determined noninvasively from simultaneous measurements of aortic flow and carotid pressure was elevated (66 +/- 26%) at 0.5 h postexercise (P = 0.04), followed by a decline to baseline 1 h after exercise. Aortic pulse-wave velocity, which is inversely related to compliance, was reduced (4 +/- 2%; P = 0.04) at 0.5 h postexercise. Pulse-wave velocity in the leg decreased by 10 +/- 4% at this time (P = 0.01). Mean arterial pressure was unchanged; however, central systolic blood pressure was reduced postexercise (P = 0.03). Cardiac output was elevated after exercise (P = 0.007) via heart rate elevation (P = 0.001), whereas stroke volume was unchanged. Total peripheral resistance was therefore reduced (P = 0.01) and would be expected to contribute to an elevation in arterial compliance. In conclusion, a single bout of cycling exercise increased whole body arterial compliance by mechanisms that may relate to vasodilation.

Adult↗

PubMed1997

Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability.

The compliance or elasticity of the arterial system, an important index of circulatory function, diminishes with increasing cardiovascular risk. Conversely, systemic arterial compliance improves through eating of fish and fish oil. We therefore tested the value of high intake of alpha-linolenic acid, the plant precursor of fish fatty acids. Fifteen obese people with markers for insulin resistance ate in turn four diets of 4 weeks each; saturated/high fat (SHF), alpha-linolenic acid/low fat (ALF), oleic/low fat (OLF), and SHF. Daily intake of alpha-linolenic acid was 20 g from margarine products based on flax oil. Systemic arterial compliance was calculated from aortic flow velocity and aortic root driving pressure. Plasma lipids, glucose tolerance, and in vitro LDL oxidizability were also measured. Systemic arterial compliance during the first and last SHF periods was 0.42 +/- 0.12 (mean +/- SD) and 0.56 +/- 0.21 units based on milliliters per millimeter of mercury. It rose significantly to 0.78 +/- 0.28 (P < .0001) with ALF; systemic arterial compliance with OLF was 0.62 +/- 0.19, lower than with ALF (P < .05). Mean arterial pressures and results of oral glucose tolerance tests were similar during ALF, OLF, and second SHF; total cholesterol levels were also not significantly different. However, insulin sensitivity and HDL cholesterol diminished and LDL oxidizability increased with ALF. The marked rise in arterial compliance at least with alpha-linolenic acid reflected rapid functional improvement in the systemic arterial circulation despite a rise in LDL oxidizability. Dietary n-3 fatty acids in flax oil thus confer a novel approach to improving arterial function.

Arteries↗

PubMed1997

Role of Ca2+ in metabolic inhibition-induced norepinephrine release in rat brain synaptosomes.

Ischemia and simulated ischemic conditions induce enhanced release of norepinephrine (NE) in the brain and the heart. Although studies with neuronal preparations demonstrated a rise in [Ca2+]i under energy-depleted conditions, such release of NE in the heart appears to be predominantly Ca2+ independent. Since Ca2+ overload occurs in ischemia or energy depletion and since a rise in [Ca2+]i triggers exocytosis without membrane depolarization, we tested the possibility, using brain synaptosomes, that increased NE release could be, at least in part, a consequence of raised [Ca2+]i. Brain synaptosomes were incubated with Krebs-Henseleit medium, and ischemia was mimicked by treatment with metabolic inhibitors. NE content in incubation medium (supernatant) and synaptosomes was analyzed chromatographically. Treatment with metabolic inhibitors reduced ATP content by 75% and increased [Ca2+]i by more than fourfold within minutes. Metabolic inhibition elicited NE release, which started within 10 minutes and reached a maximum after 30 minutes, with a corresponding 55% reduction in synaptosomal NE content after 40 minutes. NE release, together with a marked increase in [Ca2+]i, was also induced in energy-depleted synaptosomes by Ca2+ repletion after incubation with the Ca(2+)-free medium. Effects on NE release of various interventions to prevent Ca2+ overload were tested. Omission of Ca2+ from the incubation medium or loading synaptosomes with the Ca2+ chelator BAPTA-AM (20 and 100 mumol/L) prevented NE release, indicating a Ca(2+)-dependent mechanism. Inhibition of Ca2+ channels with omega-conotoxin, cadmium, or nifedipine had no effect on NE release during energy depletion. In contrast, nickel and 3,4-dichlorobenzamil, Na(+)-Ca2+ exchange inhibitors, dose-dependently inhibited NE release. In conclusion, this study provides evidence that under energy-depleted conditions, Ca2+ overload in synaptosomes of noradrenergic neurons from the brain is an important mechanism for the enhanced release of NE and that a reversal of Na(+)-Ca2+ exchange may be the key pathway leading to intraneuronal Ca2+ overload.

Animals↗

PubMed1997

Risk factors for coronary heart disease in a population with a high prevalence of obesity and diabetes: a case-control study of the Polynesian population of Western Samoa.

OBJECTIVE: To evaluate anthropometric, haemodynamic and biochemical risk markers for coronary heart disease (CHD) in the Polynesian population of Western Samoa in a case-control study of 43 cases of CHD compared with 90 age- (mean 53 years) and sex-matched controls. METHODS: Cases were identified on the basis of a 12-lead electrocardiogram and clinical history. RESULTS: More than 60% of the participants had a body mass index > or =30 kg/m2 and nearly 80% had central obesity. Both diabetes mellitus (17%) and impaired glucose tolerance (9%) were also common in this population. Nineteen per cent of the population were hypertensive and both antihypertensive therapy (21 versus 1%, P<0.001, risk 23.6) and hypertension (35 versus 11%, P<0.01, risk 4.3) were significantly more common among cases than they were among controls. In addition, the plasma high-density lipoprotein cholesterol level was lower (1.00+/-0.09 versus 1.24+/-0.05 mmol/l, P<0.05) and the plasma urate level was higher (0.42+/-0.02 versus 0.37+/-0.01 mmol/l, P<0.05) in the female cases than they were in their respective controls. Low-density lipoprotein (LDL) particle sizing did not reveal an excess of small LDL particles to be a feature of CHD cases, but more than 70% both of cases and of controls had multiple LDL species. The response of the triglyceride level to a fat-rich meal was the same for CHD cases and controls. CONCLUSION: The population studied had a high prevalence of several risk factors for CHD, including obesity and non-insulin-dependent diabetes mellitus; however, the most prominent factor relating to CHD within the community was the presence of hypertension.

Adult↗

PubMed1996

Arrhythmogenic action of thrombin during myocardial reperfusion via release of inositol 1,4,5-triphosphate.

BACKGROUND: Cardiac reperfusion initiates release of inositol 1,4,5-triphosphate [Ins(1,4,5)P3] and arrhythmogenesis via norepinephrine stimulation of alpha1-adrenergic receptors. The present study examines arrhythmogenic effects of thrombin-stimulated Ins(1,4,5)P3 release under these conditions. METHODS AND RESULTS: [3H]Ins(1,4,5)P3 release was measured in [3H]inositol-labeled rat hearts by high-performance liquid chromatography. Arrhythmia studies were performed in buffer-perfused rat hearts. Two-minute reperfusion after 20 minutes of global ischemia increased [3H]Ins(1,4,5)P3 from 1123 +/- 77 to 2238 +/- 44 cpm/mg tissue. No increase was observed in catecholamine-depleted hearts (755 +/- 89 cpm/mg). The addition of thrombin (5 IU/mL) or thrombin receptor agonist peptide (TRAP(1-6), 50 micromol/L) restored the reperfusion Ins(1,4,5)P3 response (thrombin, 1518 +/- 68 cpm/mg and TRAP(1-6), 1755 +/- 128 cpm/mg). Ins(1,4,5)P3 release initiated by norepinephrine or thrombin was inhibited by gentamicin (150 micromol/L; 986 +/- 52 and 868 +/- 125 cpm/mg, respectively). The thrombin response was inhibited by the phospholipase C inhibitor U-73122 (5 micromol/L; 394 +/- 59 cpm/mg) but not by its inactive isomer U-73343. The norepinephrine response was not inhibited by U-73122 (2126 +/- 74 cpm/mg). Ventricular tachycardia and ventricular fibrillation were observed in intact hearts but not in hearts from catecholamine-depleted rats (ventricular fibrillation duration, 110 +/- 19 versus 0 +/- 0 seconds). The addition of thrombin or TRAP(1-6) increased arrhythmias in catecholamine-depleted hearts (112 +/- 32 and 89 +/- 28 seconds, respectively). Gentamicin and U-73122 but not U-73343 prevented thrombin-induced arrhythmias. Gentamicin inhibited norepinephrine-initiated arrhythmias, but U-73122 was ineffective. CONCLUSIONS: This study demonstrates that the development of reperfusion arrhythmias under these conditions depends on the release of Ins(1,4,5)P3.

Animals↗

PubMed1996

Enhanced vasodilation to acetylcholine in athletes is associated with lower plasma cholesterol.

We investigated a change in vascular reactivity as a potential adaptive mechanism to chronic exercise. The study consisted of 2 separate protocols with 10 male athletes and 10 age-matched sedentary male control subjects participating in each. Protocol 1 investigated forearm blood flow responses to intra-arterial infusions of acetylcholine and sodium nitroprusside by use of venous occlusion plethysmography. Protocol 2 used identical techniques to study responses to norepinephrine, angiotensin II (ANG II), and NG-monomethyl-L-arginine (L-NMMA). The percent reduction in forearm vascular resistance to acetylcholine was significantly greater in the athletic compared with the sedentary group (multivariate analysis of variance for repeated measures, P = 0.03). Covariance analysis suggested that the lower total cholesterol level of the athletic group (P = 0.03) may contribute to their enhanced responsiveness to acetylcholine. There were no differences between athletic and sedentary groups in the forearm vascular resistance responses to norepinephrine, ANG II, sodium nitroprusside, or L-NMMA. These data support the hypothesis that long-term endurance training is associated with enhanced endothelium-dependent dilator reserve due to altered lipoprotein levels in athletes. This finding may have therapeutic application in conditions of elevated cholesterol and impaired vasodilator capacity including hypertension, hypercholesterolemia, atherosclerosis, and cardiac failure.

Acetylcholine↗

PubMed1996

Response to cardiac sympathetic activation in transgenic mice overexpressing beta 2-adrenergic receptor.

Transgenic mice have been created with 200-fold overexpression of beta 2-adrenergic receptors specifically in the heart. Cardiac function was studied in these transgenic mice and their controls at baseline and during isoproterenol perfusion or sympathetic nerve stimulation. The model used was an in situ buffer-perfused, innervated heart, and the left ventricle maximal derivative of pressure over time (dP/dtmax) and heart rate (HR) were measured. Basal HR and dP/dtmax were 30-40% higher in hearts from transgenic mice than controls. Electrical stimulation of sympathetic nerves (2, 4, and 8 Hz) or infusion of isoproterenol markedly increased HR and dP/dtmax in control hearts. Hearts from transgenic mice did not respond to isoproterenol. However, hearts from transgenic mice retained the HR response to nerve stimulation, and a small increase in dP/dtmax was also detected. Atenolol inhibited the response to nerve stimulation in control hearts but not that in hearts from transgenic mice. ICI-118551 inhibited the response in transgenic hearts. Basal HR and dP/dtmax were decreased by ICI-118551 only in transgenic hearts. Thus overexpression of cardiac beta 2-receptors modifies beta-adrenergic activity, but the responses to endogenous and exogenous adrenergic stimulation are affected differently.

Adrenergic beta-Agonists↗

PubMed1996

Dietary fish oil prevents reperfusion Ins(1,4,5)P3 release in rat heart: possible antiarrhythmic mechanism.

Dietary enrichment with fish oil-derived n-3 polyunsaturated fatty acids has been shown to suppress the arrhythmias that occur during postischemic reperfusion. We have recently implicated a rapid release of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] during postischemic reperfusion in the generation of these arrhythmias. The effects of dietary supplementation with fish oil on both cardiac Ins(1,4,5)P3 and arrhythmogenic responses to reperfusion were therefore investigated in perfused rat hearts. Comparisons were made with control and n-6 polyunsaturated or saturated fat-supplemented diets. In control hearts, reperfusion increased Ins(1,4,5)P3 levels [from 9 +/- 2 at 20 min ischemia to 26 +/- 3 counts per minute (cpm)/mg protein with 2 min of reperfusion] and produced a high incidence of ventricular tachycardia (92% VT) and ventricular fibrillation (85% VF). Dietary fish oil supplementation, which increased composition of n-3 fatty acids in myocardial membrane phospholipids, prevented the reperfusion-induced rise in Ins(1,4,5)P3 (11 +/- 1 at 20 min ischemia and 12 +/- 2 cpm/mg protein after 2-min reperfusion) and significantly suppressed reperfusion arrhythmias (38% VT, 13% VF; P < 0.01 vs. control group). Thus the inhibition of reperfusion-induced rises in Ins(1,4,5)P3 by n-3 polyunsaturated fatty acids after dietary fish oil supplementation provides a possible mechanism for the inhibitory effect of n-3 fatty acids on reperfusion-induced arrhythmias.

Adenosine Triphosphate↗

PubMed1996

Systemic arterial compliance is decreased in newly-diagnosed patients with coronary heart disease: implications for prediction of risk.

BACKGROUND: Proximal aortic compliance has been shown to be lower in coronary heart disease (CHD) patients compared with healthy matched controls. Assessment of proximal systemic compliance can be performed non-invasively and, therefore, the measurement of proximal compliance may be useful as a risk marker of the likelihood of significant coronary disease. METHODS: Systemic arterial compliance (SAC) and regional aortic stiffness (beta-index of the transverse arch) were measured non-invasively in a group of 20 newly-diagnosed CHD subjects and compared with an otherwise matched control group. These measurements were used to obtain an estimate of the predictive power of mechanical indices in CHD. RESULTS: Significant differences between subjects and controls were found in both SAC and regional aortic stiffness in the absence of differences in blood pressure. Use of loge(SAC) resulted in correct identification of 60% of the cases and 85% of controls. Use of both mechanical indices improved discrimination to 100% for cases, and 87% for controls. Equal likelihood points (case/control), derived from the estimated group distributions, corresponded to loge(SAC) = -1.30 and loge (beta-index) = -2.25. Arbitrarily requiring a 20:1 odds ratio of lack of disease required loge(SAC) > -1.40 and loge (beta-index) < 2.25. For the same odds ratio of presence of disease, loge(SAC) < -2.70 and loge (beta-index) > 3.50 were required. CONCLUSION: Non-invasive assessment of aortic elastic properties is not a definitive diagnostic test for CHD. Our results demonstrate the potential for repeatable, non-invasive methods of assessment of arterial mechanical properties to provide useful additional information for the overall assessment of an individual's cardiovascular risk. Our results also provide a basis for selecting arbitrary break points by which to group subjects in prospective studies.

Aorta↗

PubMed1995

Suppression of ventricular arrhythmias during ischemia-reperfusion by agents inhibiting Ins(1,4,5)P3 release.

BACKGROUND: Reperfusion following myocardial ischemia causes a rapid and transient release of inositol (1,4,5)triphosphate [Ins(1,4,5)P3]. The aim of this study was to test whether this increased Ins(1,4,5)P3 release was important for the development of ventricular arrhythmias and whether agents that inhibit this signal transduction pathway, such as aminoglycoside antibiotics, suppress arrhythmias. METHODS AND RESULTS: In perfused rat hearts, ventricular tachycardia (VT), ventricular fibrillation (VF), and accumulation of Ins(1,4,5)P3 were measured during early reperfusion. A number of different compounds, including neomycin, gentamicin, streptomycin, spermine, reserpine, and prazosin, were effective in inhibiting the reperfusion-induced Ins(1,4,5)P3 release and the onset of VT and VF in parallel. A strong correlation existed between Ins(1,4,5)P3 content, measured at 2 minutes of reperfusion, and the incidence of reperfusion VT and VF. In addition, intravenous gentamicin suppressed the onset of arrhythmias under ischemic and reperfusion conditions in vivo. CONCLUSIONS: Our results are consistent with the view that Ins(1,4,5)P3 release plays a pivotal role in mediating arrhythmias during early reperfusion. Agents inhibiting Ins(1,4,5)P3 release are antiarrhythmic and may have potential use clinically.

Alkaloids↗

PubMed1995

Sympatholytic action of intravenous amiodarone in the rat heart.

BACKGROUND: Amiodarone is a commonly used antiarrhythmic agent with complex pharmacological effects. Although ventricular arrhythmias can be suppressed soon after intravenous amiodarone, the mechanisms responsible for this action are unclear. We studied the effects of acute treatment with amiodarone on the metabolism and release of norepinephrine (NE) in intact rats and in perfused rat hearts. METHODS AND RESULTS: Experiments were performed in anesthetized rats and in perfused, innervated hearts with amiodarone administered intravascularly. NE release was induced by electrical stimulation of the sympathetic ganglion. Concentrations of NE and its intraneuronal metabolite dihydroxyphenylglycol (DHPG) in hearts, plasma, and coronary venous effluent were measured by high-performance liquid chromatography. Acute administration of amiodarone induced dose-dependent increases in DHPG concentrations in plasma (5 mg/kg, +48%; 15 mg/kg, +84%; and 50 mg/kg, +467%) and in coronary venous effluent (1 mumol/L, +37%; 3 mumol/L, +510%; and 10 mumol/L, +1100%) together with an unchanged basal overflow of NE. In perfused hearts, NE release evoked by nerve stimulation was inhibited by infusion of amiodarone (1 mumol/L, -16%; 3 mumol/L, -24%; and 10 mumol/L, -64%) or by intravenous amiodarone (50 mg/kg) given 1 hour before heart perfusion (-70%), and the extent of this suppression correlated well with levels of DHPG overflow present immediately before nerve stimulation. When given in vitro and in vivo, amiodarone also significantly reduced NE and increased DHPG content in the heart, leading to a raised DHPG/NE ratio. All these effects of amiodarone were similar to those found with reserpine but less potent. In contrast, oral amiodarone produced none of these effects. CONCLUSIONS: Acute administration of amiodarone in perfused hearts or intact rats induces partial NE depletion in the heart by interfering with vesicular NE storage and enhancing intraneuronal NE metabolism, effects associated with an impaired NE release during sympathetic activation. Oral dosing with amiodarone has no such effect. Further study is required to test whether this novel sympatholytic effect of amiodarone contributes to its antiarrhythmic action after intravenous administration.

Administration, Oral↗

PubMed1995

Determinants of arterial stiffness in Chinese migrants to Australia.

The determinants of arterial properties in Chinese migrants to Australia were evaluated. Fifty-eight migrants had recently arrived while 25 were long term residents. All were apparently free of cardiovascular disease. In addition to ultrasound determination of the stiffness of the thoracic aorta, measurements were also made of pulse wave velocities in the trunk and limbs. Factors investigated as potential determinants of arterial properties included age, sex, blood pressure, plasma lipids, urinary electrolyte excretion and duration of residence in Australia. Aortic PWV (PWVAF), PWV from the femoral to dorsalis pedis artery (PWVFD) and the aortic elastic modulus Ep were all dependent on age and mean arterial pressure. Ep was additionally dependent on sodium excretion (negatively), PWVAF on LDL cholesterol (negatively) and migrant status and PWVFD on sex and potassium excretion (negatively). PWV in the arm (PWVBR) was only dependent on sex. Regional aortic stiffness Ep and PWVAF were significantly higher in the established compared with the recent migrants. Dietary differences were evident between the two migration groups, with recent migrants eating significantly more rice meals, but there were no differences in plasma total or HDL cholesterol or triglyceride concentrations. Determinants of the stiffness of the arterial circulation in disease free Chinese subjects change considerably from proximal to distal sites, with age, blood pressure and cholesterol effects being most pronounced proximally and sex and urinary potassium excretion distally. Increasing duration of Australian residence appears to be accompanied by an increase in proximal arterial stiffness.

Adult↗

PubMed1995

Effects of dietary fat supplementation on inositol phosphate release and metabolism in rat left atria.

Eight weeks dietary supplementation with oils enriched in saturated fats, n-6 polyunsaturated fats and n-3 polyunsaturated fats resulted in a reduced inositol phosphate response in isolated rat left atria. Reductions in both basal activity and norepinephrine-stimulated activity were observed. Diets supplemented with n-3 polyunsaturated fats produced a greater decrease in the norepinephrine-stimulated release than the other dietary groups. In addition, supplementation with n-6 polyunsaturated fats resulted in higher levels of the Ca(2+)-releasing compound inositol(1,4,5)trisphosphate while addition of n-3 fats eliminated accumulation of inositol(1, 4)bisphosphate in response to norepinephrine. The reduction in inositol phosphate accumulation observed in all fat-supplemented groups demonstrates the need for caution in choosing relevant control groups in such dietary studies. The specific effects of n-6 and n-3 polyunsaturated fats on individual inositol phosphate isomers demonstrates subtle effects on inositol phosphate metabolism, the significance of which requires further investigation.

Animals↗

PubMed1995

How do fish oils affect vascular function?

1. This is a review on the mechanisms by which fish oils affect vascular function and how such changes contribute to their documented cardioprotective effects. 2. Evidence that fish oils depress vascular responses to contractile agents will be examined. It is concluded that this effect of fish oils is mediated predominantly by alterations in prostanoid profile. 3. Effects of fish oils on arterial relaxation are discussed with particular emphasis on endothelium dependent relaxation. It is suggested that the functional impairment of endothelium dependent relaxation documented in a number of cardiovascular disease states can be reversed by dietary fish oils. 4. In addition, possible effects of fish oils on growth factors, inositol trisphosphate and lipid metabolism, the sympathetic nervous system, rheological and membrane properties and inducible nitric oxide are reviewed.

Acetylcholine↗

PubMed1995

Arterial compliance may influence baroreflex function in athletes and hypertensives.

The present study investigated arterial compliance as a possible influence on mean arterial pressure-heart rate (MAP-HR) reflex function in athletes and hypertensives. Aortic stiffness and systemic arterial compliance (SAC) were estimated in 25 elite male athletes and 25 age-matched sedentary controls. Blood pressure did not vary between groups, but SAC was higher in the athletic compared with the sedentary group (0.46 +/- 0.04 vs. 0.37 +/- 0.02 arbitrary compliance units; P = 0.03). In five hypertensives and six age-matched normals and in a subgroup of seven athletes and seven age-matched controls the sigmoidal MAP-HR reflex was assessed using phenylephrine and nitroprusside. In athletes compared with sedentary subjects MAP-HR reflex sensitivity was the same; however, the maximum tachycardia in response to blood pressure reduction was lower in the athletic group (87.1.1 +/- 3.7 vs. 97.1 +/- 2.9 beats/min; P = 0.05). Athletes had a higher blood pressure corresponding to 95% of the HR range (64.2 +/- 3.2 vs. 54.0 +/- 2.1 mmHg; P = 0.02), but there was no difference in the blood pressure corresponding to 5% of the HR range. The blood pressure excursion necessary to traverse the baroreceptor transducer range (MAPd) was therefore less in athletes compared with normals. The beta-index of aortic stiffness correlated closely with MAPd (R = 0.70; P < 0.01). In hypertensives reflex sensitivity was reduced, the minimum HR was elevated, and the MAPd was 56% greater compared with normals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Inositol phosphate release and metabolism during myocardial ischemia and reperfusion in rat heart.

A detailed study of the effects of global myocardial ischemia and reperfusion on inositol phosphate release and metabolism has been undertaken by using isolated perfused rat hearts. Ischemia for longer than 5 minutes caused a cessation of inositol phosphate production, with inositol phosphates initially present accumulating as isomers of inositol monophosphate. This inhibition was independent of norepinephrine. In contrast, 2-minute reperfusion following 20-minute ischemia produced a rapid and transient release of inositol phosphates that was dependent on the release of norepinephrine and mediated by alpha 1-adrenergic receptors. By a number of criteria, this reperfusion response was different from the norepinephrine response in normoxic tissue. First, total release of inositol phosphates was greater (466 +/- 37 compared with 345 +/- 29 cpm/mg protein, P < .05). Second, inositol 1,4,5-trisphosphate was released with postischemic reperfusion (103 +/- 18 to 207 +/- 11 pmol/mg protein), whereas release was not detected in normoxic myocardium. In agreement with this, neomycin (0.5 and 5 mmol/L) inhibited inositol phosphate release only under reperfusion conditions. Third, the reperfusion response, unlike the response in nonischemic tissue, required extracellular Ca2+. Longer periods of reperfusion resulted in a return to a pattern of inositol phosphate release that was not different from that seen in normoxic tissue. The rapid and transient release of inositol 1,4,5-trisphosphate at 2-minute postischemic reperfusion provides an explanation for the enhanced role of alpha 1-adrenergic receptors under these conditions and suggests an important role for this compound in initiating reperfusion-induced pathological events.

Animals↗

PubMed1995

Cardiovascular protection by oestrogen is partly mediated through modulation of autonomic nervous function.

Experimental studies have provided evidence that the autonomic nervous activity is modulated by oestrogen. Such modulation at central and peripheral levels tends to suppress sympathetic but elevate parasympathetic tone to the cardiovascular system. Thus, available data support the view that cardiovascular protection by oestrogen may, at least in part, be mediated by its influence on autonomic nervous function.

Adult↗