Search PubMed⌕ Search

Biomedical subjects

P Vallance

Publications and source records attributed to P Vallance.

At least 145 records · Page 8Linked to original sources
PubMed1991

Hyperdynamic circulation in cirrhosis: a role for nitric oxide?

Hypotension, low systemic vascular resistance, and a reduced sensitivity to vasoconstrictors are features of cirrhosis. These cardiovascular changes might be the result of increased synthesis of a vasodilator. Nitric oxide (NO), a potent vasodilator, is synthesised in and released from peripheral blood-vessels in man. Studies in animals indicate that bacterial endotoxin and cytokines induce NO synthase expression in vessel walls, with sustained NO release and consequent hypotension. Endotoxaemia is a common feature of cirrhosis; persistent induction of NO synthase may account for the associated haemodynamic changes.

Amino Acid Oxidoreductases↗
PubMed1991

Dilator actions of arginine in human peripheral vasculature.

1. L-Arginine is the physiological precursor for the formation of endothelium-derived nitric oxide. The synthesis of nitric oxide is stereospecific: D-arginine is not a substrate for nitric oxide synthase. It is possible that the provision of excess L-arginine substrate might increase the vascular synthesis of nitric oxide. We have examined this possibility by studying the effects of local infusion of L- and D-arginine in the forearm resistance bed and the superficial dorsal hand veins of healthy subjects. 2. Drugs were either infused locally into a vein on the back of the hand and then the vein diameter was measured using a linear displacement technique, or into the brachial artery and then the forearm blood flow was measured by venous occlusion plethysmography. 3. In the superficial hand veins, L- and D-arginine free base and L- and D-arginine hydrochloride (all four preparations at a dose of 5 mumol/min) all caused a significant increase in venous diameter. The responses of the L- and D-enantiomers did not differ significantly from one another. 4. In the forearm resistance bed, L- and D-arginine free base and L- and D-arginine hydrochloride were without effect at doses of 10 and 40 mumol/min. However, at doses of 160 mumol/min all three preparations of arginine caused a significant increase in forearm blood flow compared with control values. The responses to the three preparations of arginine did not differ significantly from one another. 5. These results show that arginine in high dose is a vasodilator in both human resistance vessels and superficial veins in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Biphasic response to acetylcholine in human veins in vivo: the role of the endothelium.

1. The dose-response to acetylcholine has been examined in dorsal hand veins of healthy volunteers before and after removal of the endothelium. 2. Measurements were made in single dorsal hand veins during local infusions of acetylcholine. The vein was irrigated with distilled water to remove the endothelium. Dilator studies were performed in vessels preconstricted by a continuous infusion of noradrenaline. 3. In the endothelium-intact vessel the dose-response to acetylcholine was biphasic; low doses produced venodilatation with higher doses causing venoconstriction. 4. Dilatation to low doses of acetylcholine was abolished by prior irrigation with distilled water, consistent with denudation of the endothelium by this process. Irrigation augmented the constriction seen in response to higher doses of acetylcholine. 5. This is the first demonstration of an endothelium-dependent biphasic dose-response to acetylcholine in man. The results raise questions as to the possible physiological actions of endogenous acetylcholine and as to the use of the acetylcholine dose-response curve as a marker of endothelial function.

Acetylcholine↗
PubMed1989

Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man.

NG monomethyl-L-arginine (L-NMMA), a specific inhibitor of the synthesis of endothelium-derived nitric oxide (NO), was infused into the brachial arteries of healthy volunteers to study the role of NO in the control of forearm blood flow. L-NMMA caused a 50% fall in basal blood flow and attenuated the dilator response to infused acetylcholine but not that to glyceryl trinitrate. These results indicate that the dilator action of endothelium-derived NO contributes to the control of basal and stimulated regional blood flow in man. Impairment of production of NO might account for the abnormalities in vascular reactivity that characterise a wide variety of disease states.

Acetylcholine↗
PubMed1989

The interplay between platelet and vessel-wall mediators in coronary artery occlusion.

Myocardial infarction (MI) is associated with platelet aggregation and coronary vasospasm. Endogenous mediators produced by platelets and the vessel wall alter platelet function and smooth muscle tone and may be involved in the infarctive process. The synthesis and actions of these mediators is largely determined by interactions between platelets and the vessel-wall. MI occurs at sites of endothelial cell damage where the balance of mediators is shifted in favour of aggregation and vasospasm. Therapeutic intervention should aim at restoring the balance of mediators, and this will involve manipulation of endothelium-derived nitric oxide or its intracellular second messengers.

Biological Factors↗
PubMed1989

Nitric oxide synthesised from L-arginine mediates endothelium dependent dilatation in human veins in vivo.

Endothelium derived relaxing factor (EDRF) has been identified as nitric oxide, synthesised from the amino acid L-arginine, a process which is inhibited by the L-arginine analogue NG-monomethyl L-arginine (L-NMMA). We have studied the effect of local infusions of L-NMMA on venous reactivity in healthy volunteers. Studies were performed using the veins on the back of the hand. The diameter of a single dorsal hand vein was measured in healthy subjects who had taken 600 mg of aspirin 30 min before the experiment. Changes in diameter were recorded during local infusions of noradrenaline, bradykinin, acetylcholine, glyceryl trinitrate, L- and D-arginine and its NG-monomethyl derivatives. L-NMMA (100 nmol.min-1) stereospecifically inhibited vasodilatation induced by acetylcholine and bradykinin (p less than 0.02) but not that induced by the endothelium independent vasodilator glyceryl trinitrate. L-NMMA (100 nmol.min-1) potentiated the venoconstrictor effect of a high dose of acetylcholine (100 nmol.min-1) without affecting the action of noradrenaline and without having a direct venoconstrictor effect in doses up to 10 mumol.min-1. These results show that the venous effects of certain vasodilators in man are mediated through the release of nitric oxide (EDRF) synthesised from L-arginine. They also highlight differences in basal and stimulated production of nitric oxide between arteries and veins.

Adult↗
PubMed1989

The potassium channel opening drug cromakalim produces arterioselective vasodilation in the upper limbs of healthy volunteers.

1. The effect of the K+ channel opening drug cromakalim on forearm blood flow during direct infusion into the brachial artery, and on the size of noradrenaline preconstricted hand veins during infusion directly into the vein, was studied in eight healthy volunteers. 2. Cromakalim (0.01-10.0 micrograms min-1) produced a dose-dependent increase in blood flow in the infused forearm, from 5.4 +/- 2.5 to 15.1 +/- 7.3 ml 100 ml-1 forearm min-1 at 10 micrograms min-1 (P less than 0.001). The half-time of offset of its action was 30 min. There was no change in blood flow in the non-infused forearm. 3. There was no increase in the size of noradrenaline pre-constricted dorsal veins during local infusion of cromakalim (0.001-1.0 microgram min-1). Glyceryl trinitrate (0.4 microgram min-1) however, completely reversed the constriction to noradrenaline (P less than 0.001). 4. The clear arterioselectivity of cromakalim, as with other members of this new class of drug, accords with the dependency of venoconstriction on receptor-operated, rather than potential-operated mechanisms which are of importance in resistance vessels. With this haemodynamic profile cromakalim may prove of value in the treatment of arterial hypertension.

Adult↗
PubMed1989

Asthma and chronic airflow limitation in the highlands of Papua New Guinea: low prevalence of asthma in the Asaro Valley.

The prevalence of asthma in the South Fore region of Papua New Guinea was found to be 7.3%, which is thought exceptionally high for highland areas in this country. To investigate the prevalence of asthma and of chronic airflow limitation in a different highland region with similar living conditions, adults and children from 7 villages in the Asaro Valley were interviewed. Questions were asked about smoking history and about past and present symptoms of cough, of shortness of breath, of chest tightness and of asthma. Of 743 adults interviewed, 206 underwent a clinical study with measurements of lung function, bronchial responsiveness and skin prick tests. Dust was collected from the floors and blankets of 36 houses for counts of house dust mites. We did not find any children with symptoms of asthma. Only 2 adults (0.3%) had symptoms consistent with asthma, and a further 6.2% had symptoms and/or lung function consistent with chronic airflow limitation. Most bronchial hyperresponsiveness was associated with asthma or with chronic airflow limitation. The prevalence of atopy was similar in the Asaro and South Fore populations, but the South Fore had higher house dust mite counts in blanket dust. The low prevalence of asthma in the Asaro Valley is unexplained in terms of factors normally associated with asthma. Because asthma in this area does not appear in childhood and only develops in a small proportion of adults, it may be of different aetiology to asthma in Caucasian populations.

Adult↗
PubMed1988

Prospective study of mortality associated with chronic lung disease and smoking in Papua New Guinea.

In Papua New Guinea a 15-year mortality follow-up was carried out among 2026 highlanders and 1734 coastal dwellers on whom data on respiratory symptoms and signs, and lung function had been obtained by prevalence surveys in 1970/71. Survival status was established in 99%, of whom 9.8% had died, the rate being higher in the highland (12.2%) than in the coastal population (7.0%). All abnormalities indicative of chronic lung disease were associated with increased mortality though this was statistically significant only for chronic shortness of breath (SMR 195) and wheezing (SMR 183) in coastal females. In those aged 25 years or more there was a strong association between reduced lung function (FEV1, FVC, FEV1/FVC%) and mortality, after controlling for age and height. The associations observed were as strong as those reported from prospective studies in developed countries. The most striking difference was that in Papua New Guinea mortality showed no association whatever with tobacco smoking; this may be because the traditional type of tobacco and method of smoking it resembles pipe/cigar smoking in developed countries.

Adolescent↗
PubMedDate not supplied

Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock.

Hypotension during septic shock, which may reflect increased synthesis of the potent vasodilator nitric oxide (NO), is often refractory to vasoconstrictors. We describe the effects of NO synthase inhibition in two patients with life-threatening septic shock in whom conventional therapy had failed to restore blood pressure. NG-monomethyl-L-arginine (L-NMMA) caused dose-dependent increases in blood pressure and systemic vascular resistance in both patients, and a similar effect was observed in the second patient after treatment with NG-nitro-L-arginine methyl ester (L-NAME). These findings indicate that NO synthase induction contributes to the pathogenesis of septic shock, and that inhibition of NO synthase may represent a novel therapeutic option.

Amino Acid Oxidoreductases↗
PubMedDate not supplied

Plasma nitrogen oxides and blood lactate concentrations in Ghanaian children with malaria.

Nitric oxide is an important host defence molecule as well as being a mediator in many pathophysiological processes. To investigate its role in severe malaria, we measured plasma nitrate and nitrite concentrations in 70 children with malaria (54 with severe malaria) and 48 control subjects (33 with medical conditions and 15 surgical patients). We related these measurements to plasma lactate concentrations, an established marker of disease severity in malaria. Plasma lactate levels were significantly elevated in patients with deep coma (P = 0.0007) and those with a fatal outcome, but mean nitrogen oxide concentrations were not significantly different in the 2 outcome categories and were not related to depth of coma (P > 0.5). In patients whose cerebrospinal fluid (CSF) was examined, lactate concentrations were elevated in fatal cases (geometric mean 8.2 mmol/L, n = 5) compared with survivors (3.4 mmol/L, n = 13; P = 0.032); corresponding CSF nitrogen oxide concentrations were 10.7 microM in fatal cases compared with 12.5 microM in survivors (P = 0.5). Plasma nitrogen oxide concentrations were negatively correlated with admission parasitaemia (r = -0.41, n = 70; P < 0.0001). In our population, elevations of plasma lactate, but not nitrite or nitrate, reflected disease severity in malaria.

Biomarkers↗