bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol And Endothelial Function: A Brief Review
Authors: Puddey IB , Zilkens RR , Croft KD , Beilin LJ 
Published: March 2003

SUMMARY1. In spite of the dose‐related effects of alcohol consumption to increase blood pressure, regular light to moderate alcohol intake appears to confer protection against both coronary artery disease and ischaemic stroke. In contrast, heavy alcohol consumption increases the risk of coronary artery disease and the risk of both haemorrhagic and ischaemic stroke.2. Effects of alcohol consumption on endothelial cell function may be relevant to these disparate effects on cardiovascular outcomes. In in vitro animal studies, low doses of alcohol have been demonstrated to increase release of nitric oxide and augment endothelium‐mediated vasodilatation, whereas higher doses impair endothelium‐dependent relaxation responses. In contrast, chronic administration of alcohol to rats has generally been associated with tolerance to the acute inhibitory effects of alcohol on endothelium‐mediated vasodilatation and may even result in augmentation of such responses.3. The few human studies to date that have examined the effects of alcohol on endothelial function have focused on postischaemic flow‐mediated dilation of the brachial artery (FMD). Although blunted FMD responses have been reported in alcoholic subjects, acute administration of alcohol or short‐term interventions to reduce alcohol intake have had no effect to either improve or impair FMD.4. Further studies in humans assessing acute and longer term dose‐related effects of alcohol on endothelial function in both conduit and resistance vessels will be necessary if the relevance of the findings from in vitro and in vivo animal studies are to be understood in the context of the complex interrelationships of alcohol with cardiovascular disease.
Phenotypic And Genetic Heterogeneity Of Familial Hyperkalaemic Hypertension (Gordon Syndrome)
Authors: Achard Jean‐Michel , Disse‐Nicodeme Sandra , Fiquet‐Kempf Béatrice , Jeunemaitre Xavier 
Published: March 2003

SUMMARY1. Familial hyperkalaemic hypertension (FHH), also called pseudohypoaldosteronism type II (PHA2) or Gordon syndrome, is a rare Mendelian‐form of low‐renin hypertension. The first cases of FHH were reported approximately 30 years ago and they described the peculiar biochemical abnormalities (i.e. hyperkalaemia and hyperchloraemic acidosis despite a normal glomerular filtration rate).2. Since then, more than 90 single cases and families have been reported in the literature. These various reports show marked differences in phenotype.3. Our group has now collected 14 unrelated pedigrees originating from different parts of France and Europe. We confirm the large variations in the age of discovery and in the severity of the biochemical abnormalities from one individual to another and from one family to another one.4. Blood pressure levels have no significant relationship with hyperkalaemia or hyperchloraemia, but there is a positive relationship with age, as in the normal population.5. Analyses of clinical features and Mendelian segregation in our families demonstrate autosomal‐dominant inheritance, as expected from the literature.6. Efforts have been made in the past years to unravel the gene responsible for the disease. Until now, a primary responsability of the gene encoding the thiazide‐sensitive Na–Cl cotransporter (SLC12A3) has been excluded in PHA2 families. Three loci have been identified on chromosomes 1 (PHA2A), 17 (PHA2B) and 12 (PHA2C).7. More recently, analysis of three additional pedigrees, including 10 affected subjects, with over 25 members allowed us to demonstrate further genetic heterogeneity and the existence of at least a fourth locus.8. The genetic heterogeneity of this syndrome, and thus the variety of molecular defects, suggests the role of either several new components of the same pathway, multiple aldosterone‐ regulated effectors or direct or indirect partners of the Na–Cl cotransporter.
Role Of Nitric Oxide In Mediating Vasodilator Responses To Opioid Peptides In The Rat
Authors: Champion Hunter C , Bivalacqua Trinity J , Zadina James E , Kastin Abba J , Hyman Albert L , Kadowitz Philip J 
Published: March 2003

SUMMARY1. Endomorphins 1 and 2, endogenous ligands for the μ‐opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have vasodilator activity in the vascular bed of the hindquarters of the rat. In the present study, the role of nitric oxide (NO), vasodilator prostaglandins and the opening of KATP channels in mediating vasodilator responses to these novel agonists was investigated in the rat.2. Under constant‐flow conditions, injections of endomorphins 1 and 2, PL017 ([N‐MePhe3,D‐Pro4]‐morphiceptin),
nociceptin and Tyr‐D‐Ala‐Gly‐MePhe‐Gly(ol)‐enkephalin (DAMGO) produced
dose‐dependent decreases in hindquarters perfusion pressure. Vasodilator responses
to endomorphin 1 and 2, acetylcholine and adrenomedullin, were attenuated by the
NO synthase inhibitor NG‐nitro‐L‐arginine methyl
ester (L‐NAME) at a time when vasodilator responses to nociceptin, adrenomedullin and the NO donor diethylamine/NO were not altered.3. Vasodilator responses to endomorphins 1 and 2, nociceptin, PL017 and DAMGO were not altered after administration of sodium meclofenamate at a time when vasodilator responses to arachidonic acid were reduced significantly or after administration of U‐37883A at a time when vasodilator responses to levcromakalim were reduced significantly.4. The results of these studies indicate that vasodilator responses to endomorphins 1 and 2, PL017 and DAMGO are mediated, in large part, by the release of NO, whereas vasodilator responses to nociceptin are mediated by an L‐NAME‐insensitive
mechanism. Moreover, these results demonstrate that the vasodilator responses to
these peptides are not due to the release of vasodilator prostaglandins or the opening
of KATP channels in the hindquarters vascular bed of the rat.
Functional Roles Of KATP Channels In Vascular Smooth Muscle
Authors: Brayden Joseph E 
Published: March 2003

SUMMARY1. ATP‐sensitive potassium channels (KATP) are present in vascular smooth muscle cells and play important roles in the vascular responses to a variety of pharmacological and endogenous vasodilators.2. The KATP channels are composed of four inwardly rectifying K+
channel subunits and four regulatory sulphonylurea receptors. The KATP channels are inhibited by intracellular ATP and by sulphonylurea agents.3. Pharmacological vasodilators such as cromakalim, pinacidil and diazoxide directly activate KATP channels. The associated membrane hyperpolarization closes
voltage‐dependent Ca2+ channels, which leads to a reduction in intracellular
Ca2+ and vasodilation.4. Endogenous vasodilators such as calcitonin gene‐related peptide, vasoactive intestinal polypeptide, prostacylin and adenosine activate KATP by stimulating
the formation of cAMP and increasing the activity of protein kinase A. Part of the
mechanism of contraction of endogenous vasoconstrictors is due to inhibition of KATP channels.5. The KATP channels appear to be tonically active in some vascular beds and contribute to the physiological regulation of vascular tone and blood flow. These channels also are activated under pathophysiological conditions, such as hypoxia, ischaemia, acidosis and septic shock, and, in these disease states, may play an important role in the regulation of tissue perfusion.
Quinapril Treatment Restores The Vasodilator Action Of Insulin In Fructose‐Hypertensive Rats
Authors: Uchida Takanori , Okumura Kenji , Ito Takayuki , Kamiya Hiroki , Nishimoto Yasuhiro , Yamada Michiharu , Tomida Takahito , Matsui Hideo , Hayakawa Tetsuo 
Published: March 2003

SUMMARY1. Angiotensin‐converting enzyme (ACE) inhibitors have been shown to improve insulin‐resistance both experimentally and clinically. We therefore investigated the effects of quinapril, which has high tissue specificity for ACE, regarding the contribution of insulin to vascular contractions, as well as insulin sensitivity in a dietary rat model of insulin resistance.2. Male Sprague‐Dawley rats were divided into three groups: (i) rats fed normal chow (normal diet group); (ii) rats fed fructose‐rich chow containing 40% fructose and 7% lard (fructose diet group); and (iii) rats fed fructose‐rich chow plus quinapril (10 mg/kg per day; quinapril‐treated group).3. After 2 weeks, we evaluated systolic blood pressure, insulin sensitivity as assessed by steady state plasma glucose (SSPG) levels, response of aortic rings to phenylephrine (10–9 to 10–6 mol/L) in the presence or absence of insulin and the response of aortic rings to acetylcholine.4. Feeding rats fructose‐rich chow resulted in an elevation of blood pressure (P < 0.01) and SSPG levels (P < 0.01). Quinapril treatment significantly prevented increases in both blood pressure and SSPG, with a return to the levels seen in the normal diet group.5. In the absence of insulin, the maximal contractile response to phenylephrine did not differ between the three groups. However, in the presence of insulin (100 mU/mL), the contractile response to phenylephrine (10–6 mol/L) was reduced by 22.8 ± 1.2% in the normal diet group, although no insulin effects were observed in the fructose diet group (P < 0.01). Quinapril restored the inhibitory effect of insulin on phenylephrine‐induced contractions.6. In addition, the reduction in relaxation induced by acetylcholine in the fructose diet group was significantly reversed by quinapril treatment.7. It is concluded that the fructose diet impairs the vasodilator effects of insulin as well as acetylcholine‐induced relaxation in rat thoracic aortas. Quinapril prevented deterioration in the responses of the aortic rings, suggesting that ACE inhibitors may be useful for treating vascular insulin resistance.
Antinociceptive Action Of Captopril And Transcutaneous Electric Nerve Stimulation In Mus Musculus Mice
Authors: Motta Mauricy Alves da , Vasconcelos Mallinson da Silva , Catanho Maria Teresa de Almeida Jansen 
Published: March 2003

SUMMARY1. In the present study, the antinociceptive action of captopril was investigated, as well as its association with transcutaneous electric nerve stimulation (TENS), in mice under nociceptive stimulation.2. The modulation of abdominal contortions (writhes) produced by acetic acid was observed in order to evaluate captopril pain stimuli blockade.3. The administration of captopril produced a significant reduction of nociception, which was further reduced when captopril was associated with TENS.4. Apparently this increase in the inhibition of nociception was produced by an indirect mechanism, involving opioid liberation by TENS and an enzymatic inhibition induced by captopril and this may lead to clinical applications of captopril and TENS association in pain relief.
Effects Of Molybdenum, Silicon And Nickel On α1‐Adrenoceptor‐Induced Constriction Of Rat Isolated Aorta
Authors: Liu Dong Ling , Yan Ming , Chua Yeow Leng , Chen Chen , Lim Yean Leng 
Published: March 2003

SUMMARY1. To determine the effects of trace elements on α1‐adrenoceptor‐mediated vasoconstriction, we studied the effects of molybdenum (Mo), silicon (Si) and nickel (Ni) on vasoconstrictor response to an α1‐adrenoceptor agonist in rat aorta.2. Cumulative concentration–contraction curves were obtained for phenylephrine (1 nmol/L–10 μmol/L) in the absence and presence of Mo, Si and Ni (0.3, 1 and 3 μmol/L) in rat aorta rings. Increasing the concentration of Mo and Si from 0.3 to 3 μmol/L shifted the cumulative concentration–contraction curve to the right, but did not reduce the maximal contractile response to phenylephrine. In contrast, Ni at 1 and 3 μmol/L shifted the cumulative concentration–contraction curve to the right and, at 3 μmol/L, reduced the maximum contractile response to phenylephrine.3. We conclude that micromolar concentrations of Mo, Si and Ni affected α1‐adrenoceptor‐induced vasoconstriction and that Ni significantly inhibited the maximal contractile response to phenylephrine in rat isolated aorta.
Effects Of Caffeine On The Uncoupling Protein Family In Obese Yellow Kk Mice
Authors: Kogure Akinori , Sakane Naoki , Takakura Yasuto , Umekawa Tsunekazu , Yoshioka Keiji , Nishino Hoyoku , Yamamoto Takayuki , Kawada Teruo , Yoshikawa Toshikazu , Yoshida Toshihide 
Published: March 2003

SUMMARY1. The hypothesis that caffeine upregulates uncoupling protein (UCP)‐1, UCP‐2 and UCP‐3 expression, which contribute to thermogenesis, was investigated in obese mice.2. The mRNA levels of UCP‐1, ‐2 and ‐3 in brown adipose tissue (BAT), UCP‐2 in white adipose tissue (WAT), and UCP‐2 and ‐3 in skeletal muscle were measured using real‐time quantitative reverse transcription–polymerase chain reaction analysis in obese yellow KK mice 4 h after the subcutaneous administration of either 60 mg/kg caffeine or physiological saline. Plasma free fatty acids, adrenaline, noradrenaline and dopamine levels were also measured.3. In caffeine‐injected obese mice, UCP‐1 mRNA levels were significantly increased by 1.5‐fold in BAT, UCP‐2 mRNA levels were increased by 1.8‐ and 2.5‐fold in BAT and skeletal muscles, respectively, and UCP‐3 mRNA levels were increased 1.7‐ and 3.4‐fold in BAT and skeletal muscles, respectively, compared with control mice injected with physiological saline. There was no difference in UCP‐2 mRNA levels in WAT between the two groups.4. Plasma free fatty acids and adrenaline levels were significantly elevated in mice treated with caffeine compared with those injected with physiological saline.5. It was concluded that caffeine upregulates the expression of UCP‐1, UCP‐2 and UCP‐3 in BAT and UCP‐2 and UCP‐3 in skeletal muscles, which may contribute to thermogenesis in obese mice.
Age‐Related Changes In Dopamine D2 Receptors In Rat Heart And Coronary Vessels
Authors: Cavallotti Carlo , Nuti Federica , Bruzzone Paolo , Mancone Massimo 
Published: March 2003

SUMMARY1. The distribution of dopamine D2 receptors in rat heart and coronary vessels and the possible age‐related changes in D2 receptor density were studied. The pharmacological characteristics and the anatomical location of dopamine D2‐like receptor sites in rat heart and coronary vessels were investigated using combined binding techniques and light microscopy autoradiography.2. Samples of heart and coronary vessels were harvested from young and old rats. On frozen slices, dopaminergic D2 receptors were labelled by means of a selective D2 ligand, namely [3H]‐spiroperidol (spiperone). Inhibition studies were performed using unlabelled agonists and/or labelled and unlabelled antagonists to define pharmacological specificity of the binding. Physiological experiments were performed to demonstrate the selective antagonism between D2 receptors and many dopaminergic drugs.3. [3H]‐Spiroperidol was bound to sections of rat heart and coronary artery (in a manner consistent with the labelling of dopamine D2‐like receptors) with an equilibrium dissociation constant of approximately 2.4 ± 0.7 nmol/L and a maximum capacity of binding sites of 65.8 ± 4.5 fmol/mg protein. Experiments performed on sections of coronary veins did not allow the evaluation of specific binding. Autoradiography, observed with light microscopy, showed the development of specific silver grains within the whole wall of rat heart and coronary artery. The greater sensitivity to displacement by amisulpride, bromocriptine, domperidone, haloperidol, raclopride and L‐sulpiride than to displacement by N‐propyl‐norapomorphine, quinpirole and clozapine suggests that the binding sites observed in these experiments are likely to belong to the dopamine D2 receptor subtype.4. Comparing results in young and old rats, we observed numerous significant age‐related changes, including a decrease in D2 receptors localized in rat heart and coronary artery wall. These D2 receptors show a specific location, in close relationship with dopaminergic nerve fibres. They decrease with age and their role remains unknown.
Effects Of Birth On Baroreceptor‐Mediated Changes In Heart Rate Variability In Lambs And Fetal Sheep
Authors: Yu Ze‐Yan , Lumbers Eugenie R 
Published: March 2003

SUMMARY1. In adult unanaesthetized sheep, there is a V‐shaped relationship between mean arterial pressure (MAP) and heart rate variability (HRV), measured in both time and frequency domains. In contrast, in fetal sheep, there is only a positive direct relationship between MAP and HRV, which is determined by the cardiac vagus. We postulated that by the time lambs were 8–10 days old, the ‘adult like’ V‐shaped relationship between MAP and HRV would be present and it may appear at or after birth. To test these hypotheses, experiments were performed in six chronically catheterized fetal sheep (aged 132–138 days gestation), 10 newborn sheep (within 10 h of birth) and 10 lambs (aged 8–10 days). The relationships between MAP and HRV (in both time and frequency domains) were studied before and during β‐adrenoreceptor blockade with propranolol and before and during cardiac vagal blockade with atropine.2. In 8–10‐day‐old lambs, V‐shaped relationships between MAP and HRV (measured in both time and frequency domain) were obtained. The negative limb of this V‐shaped relationship between MAP and HRV was present after cardiac vagal blockade. The positive slope of the V was present after β‐adrenoreceptor blockade.3. In 4‐h‐old newborn sheep, there was no relationship between MAP and HRV (measured in the time domain), but between 7 and 10 h of age a negative relationship was found during treatment with atropine and a positive relationship was found during β‐adrenoreceptor blockade, when HRV was measured in both time and frequency domains.4. As described previously, there was only a positive relationship between MAP and HRV in fetal sheep, which was abolished by atropine but not affected by β‐adrenoreceptor blockade.5. Thus, until relatively late in fetal life, baroreceptor‐ modulated changes in efferent cardiac sympathetic tone, determined by measuring the effects of autonomic blockade on HRV, could not be elicited, although reflex vagal pathways were active. By 7–10 h after birth, baroreceptor‐modulated changes in efferent cardiac sympathetic tone were present. It was possible using measurements of HRV made in the time domain to show that these baroreceptor‐modulated cardiac sympathetic effects became stronger over the first 10 days of life (P < 0.01). These studies are the first to show that the influence of baroreceptor‐mediated changes in cardiac sympathetic tone on HRV increases in early life. This is probably because maturation of sympathetic innervation of the fetal sheep heart is occurring at this age.
Highly Protective Effects Of Chronic Oral Administration Of Nicorandil On The Heart Of Ageing Rats
Authors: Garnier‐Raveaud Stéphanie , Faury Gilles , Mazenot Catherine , Cand Francine , Godin‐Ribuot Diane , Verdetti Jean 
Published: March 2003

SUMMARY1. We have tested the effects of 2 month oral treatment with the KATP opener, nitric oxide (NO) donor and anti‐oxidant molecule nicorandil (0.1 mg/kg per day) on major physiological parameters and heart function of 4‐, 12‐ and 24‐month‐old rats.2. Several methods were used: (i) measurement of blood pressure using a non‐invasive tail‐cuff method; (ii) perfusion of isolated heart; (iii) lactate dehydrogenase (LDH) dosage; and (iv) measurement of monophasic action potential of rat isolated hearts.3. Blood pressure and ventricular action potential duration regularly increase with age in control animals, whereas nicorandil restores these parameters in aged animals to levels present in young adult animals. Moreover, following ischaemia, nicorandil treatment improved isolated heart survival rate (100 vs 50% for nicorandil‐treated rats and controls, respectively), heart work and left ventricular developed pressure, whereas it decreased cardiac cell damage (LDH release) and perfusion pressure.4. This condition of chronic oral nicorandil treatment presents a strong potential in the improvement of cardiac function in normal and pathological ageing.
Effect Of Kad‐1229, A Novel Hypoglycaemic Agent, On Plasma Glucose Levels After Meal Load In Type 2 Diabetic Rats
Authors: Ichikawa Kiyoshi , Yamato Tokuhisa , Ojima Kazuma , Tsuji Atsutoshi , Ishikawa Kohtaro , Kusama Hiroshi , Kojima Masami 
Published: March 2003

SUMMARY1. The effects of KAD‐1229 (a novel non‐sulphonylurea agent), voglibose (an α‐glucosidase inhibitor) and nateglinide (a non‐sulphonylurea antihyperglycaemic agent) on hyperglycaemia induced by a meal load were assessed in diabetic rats.2. KAD‐1229 suppressed the increase in plasma glucose levels seen after a meal load and the area under the curve for plasma glucose levels (AUCglucose) up to 5 h after the meal load.3. Voglibose also suppressed the increase in plasma glucose levels; however, a significant decrease in AUCglucose following voglibose was not observed.4. Nateglinide suppressed the increase in plasma glucose levels at 30 min and 1 h after the meal load; however, plasma glucose levels was above control thereafter and the AUCglucose was not decreased.5. The results indicate that KAD‐1229 has an antihyperglycaemic effect and KAD‐1229 is suggested to be a suitable agent for controlling post‐prandial hyperglycaemia.
Critical Role Of Gap Junctions In Endothelium‐Dependent Hyperpolarization In Rat Mesenteric Arteries
Authors: Goto Kenichi , Fujii Koji , Kansui Yasuo , Abe Isao , Iida Mitsuo 
Published: March 2003

SUMMARY1. Acetylcholine (ACh) evokes endothelium‐dependent hyperpolarization in arterial cells, presumably through endothelium‐derived hyperpolarizing factor (EDHF). The identity of EDHF is still elusive; however, several recent studies suggest the possible involvement of myoendothelial gap junctions in the EDHF response.2. To elucidate the role of gap junctions in endothelium‐dependent hyperpolarization, we examined the effects of the gap junction inhibitors 18α‐glycyrrhetinic
acid (18α‐GA; 10–4 mol/L) and carbenoxolone (3 ×
10–4 mol/L), a water‐soluble form of 18β‐GA, on hyperpolarization
and relaxation to ACh in rat proximal and distal mesenteric arteries. Experiments
were performed in the presence of indomethacin (10–5 mol/L) and
NG‐nitro‐L‐arginine (10–4 mol/L).3. In both proximal and distal mesenteric arteries, ACh‐induced hyperpolarization and relaxation were partially inhibited by 18α‐GA and abolished by carbenoxolone.4. Endothelium‐independent hyperpolarization to levcromakalim, an ATP‐sensitive K+ channel opener, were unaffected by 18α‐GA or carbenoxolone in both arteries.5. Relaxations to levcromakalim were unaffected by 18α‐GA, but were inhibited somewhat by carbenoxolone in proximal mesenteric arteries.6. These findings suggest that myoendothelial gap junctions play a critical role in EDHF‐mediated responses in both proximal and distal mesenteric arteries of the rat.