bluuebunny/crossref_metadata_2025 huggingface dataset:
RENAL EXTRACTION OF ATRIAL NATRIURETIC PEPTIDE IN UNILATERAL RENAL ARTERY STENOSIS
Authors: Tunny Terry J. , Gordon Richard D. , Klemm Shelley A. , Stowasser Michael , Finn Wendy L.
Published: June 2007

1. Elevated peripheral atrial natriuretic peptide (ANP) levels were observed in 12 patients with unilateral renal artery stenosis (U‐RAS).

2. Renal extraction of ANP was higher across the affected than the unaffected kidney in U‐RAS, provided the glomerular filtration rate in the affected kidney was not severely reduced (> 12 mL/min). As ANP is a high clearance compound, reduced flow on the affected side may result in increased renal extraction of ANP.

3. When glomerular filtration rate (GFR) in the affected kidney was severely reduced (<12 mL/min), renal extraction of ANP was also reduced, possibly contributing to increased circulating ANP levels in this subgroup.

4. Overall, renal extraction of ANP was inversely correlated to peripheral ANP levels in patients with U‐RAS. This might be explained by progressive sodium retention as GFR falls leading to volume expansion and increased ANP secretion.
AN ASSOCIATION OF PRIMARY ALDOSTERONISM AND ADRENALINE‐SECRETING PHAEOCHROMOCYTOMA
Authors: Gordon Richard D. , Bachmann Anthony W. , Klemm Shelley A. , Tunny Terry J. , Stowasser Michael , Storie William J. , Rutherford John C.
Published: June 2007

1. Two patients with adrenaline‐only secreting phaeochromocytomas and primary aldosteronism were studied.

2. Urinary adrenaline levels were raised and plasma adrenaline was not suppressed normally following administration of clonidine. Plasma aldosterone to plasma renin activity ratios were repeatedly elevated.

3. Both had large intra‐adrenal phaeochromocytomas visible on computerized tomography (CT) scanning. Surrounding adrenal cortical tissue contained an adenoma in one and nodular hyperplasia in the other.

4. Following removal of the adrenal gland containing the phaeochromocytoma, plasma and urinary adrenaline levels, and plasma aldosterone to plasma renin activity ratios returned to normal.

5. Adrenaline‐only secreting phaeochromocytomas and primary aldosteronism have been rarely diagnosed even as separate entities, but reliable screening tests are now available.

6. Simultaneous presence of these two conditions of hormone excess is probably a chance occurrence. Alternatively, there may be a genetic predisposition to endocrine dysplasia, or an interaction between the contiguous medullary and cortical tissues, particularly after the normal architecture has been disturbed by an enlarging phaeochromocytoma.
VASCULAR ENDOTHELIN RESPONSIVENESS AND RECEPTOR CHARACTERISTICS IN VITRO AND EFFECTS OF ENDOTHELIN RECEPTOR BLOCKADE IN VIVO IN CYCLOSPORIN HYPERTENSION
Authors: Phillips P. A. , Rolls K. A. , Burrell L. M. , Casley D. , Aldred K. L. , Hardy K. J.
Published: June 2007

1. The aim of these studies was to determine the role of endothelin in cyclosporin A ([CsA], 10 mg/kg per day, s.c., for 30 days) hypertension in the rat.

2. There were no significant differences in plasma endothelin concentrations, in vitro mesenteric vascular membrane [125I]‐endothelin‐l (ET‐1) binding characteristics or myographic vascular responses to endothelin‐1 between the CsA and control groups (systolic blood pressure 135 ± 1 vs 127 ± 1 mmHg, respectively, P<0.001).

3. Twenty‐four hours after selective endothelin type A receptor blockade in vivo with BQ123, blood pressure in CsA hypertensive rats was lowered to levels of normotensive controls.

4. These results suggest that changes in endothelin synthesis rather than changes in vascular sensitivity and/or ET‐1 receptor characteristics may contribute to CsA‐induced hypertension.
SUPPRESSION OF NITRIC OXIDE PRODUCTION BY CYCLOSPORIN A AND FK506A IN RAT VASCULAR SMOOTH MUSCLE CELLS
Authors: Akita K. , Dusting G. J. , Hickey H.
Published: June 2007

1. The effects of the immunosuppressants cyclosporin A (CsA) and FK506 on nitric oxide (NO) synthesis induced by lipopolysaccharide (LPS) or cytokines were examined in rat vascular smooth muscle cells (VSMC) in culture.

2. CsA inhibited by up to 90% the accumulation of nitrite induced by LPS, but FK506 had a weaker effect on nitrite accumulation induced by LPS in these cells. Both CsA and FK506 (at 1 μmol/L) significantly inhibited nitrite production induced by recombinant murine interleukin‐1β (rIL‐1β).

3. Given their differing potency, it is likely that CsA and FK506 suppress induction of NO synthase through different intracellular mechanisms. This action could contribute to the side effects of CsA therapy.
GLYCEROL DEHYDRATES OEDEMATOUS AS WELL AS NORMAL BRAIN IN DOGS
Authors: Wang Jia‐Yi , Chen Jiann‐Liang
Published: June 2007

1. Although the effect of glycerol on reducing intracranial pressure has been widely investigated, only a few studies have reported its dehydrating effect on brain oedema caused by infarction, ischaemia, microembolism and cold injury, but none on traumatic oedema. In this study the effects of glycerol (1 g/kg, i.v. bolus infusion at a rate of 0.04 g/kg per min) on traumatic and cryogenic cerebral oedema and on normal brain were compared in the anaesthetized dog. The tissue water content was measured with the gravimetric method.

2. Oedema resulting from mechanical trauma was initiated 4 h prior to treatment with glycerol (8 dogs) or vehicle (5 dogs) by closed head contusion with fixed force under general anaesthesia. Tissue samples underneath the region of contusion were taken, before and 1 h after infusion of glycerol or vehicle, for the measurement of water content.

3. Glycerol infusion decreased the water content in white matter of the traumatic brain model from 76.54 ± 1.70% to 70.73 ± 1.54% (P<0.001). In normal brain the reduction was from 68.42 ± 0.48% to 65.36 ± 0.39% (P<0.001). Neither vehicle nor glycerol infusion resulted in significant changes in specific gravity of the gray matter.

4. Cryogenic oedema was initiated 3 h prior to the infusion of glycerol or vehicle by applying unilaterally a brass conical cup (bottom diameter 1 cm) filled with dry ice‐acetone (‐ 65°C) to the exposed dura for 1 min. The contralateral hemisphere, which was not subjected to cold injury, was used for determination of water content of normal gray and white matter.

5. Glycerol infusion decreased the water content in the white matter of the cold‐injured region from 75.38 ± 0.69% to 72.57 ± 0.58% (P<0.001). In the normal white matter the reduction was from 68.63 ± 0.34% to 65.48 ± 0.49% (P<0.001).

6. Our data indicate that glycerol decreases water content of the white matter in traumatic and cold‐injured oedematous brain as well as in normal brain.
INHIBITION BY ETHACRYNIC ACID OF NO‐MEDIATED RELAXATIONS OF THE RAT ANOCOCCYGEUS MUSCLE
Authors: Li C. G. , Brosch S. F. , Rand M. J.
Published: June 2007

1. The effects of ethacrynic acid were studied on relaxations elicited by nitric oxide (NO), the NO‐donors sodium nitroprusside (SNP) and glyceryl trinitrate (GTN), nitrergic nerve stimulation and the NO‐independent agent papaverine in isolated preparations of rat anococcygeus muscles.

2. Ethacrynic acid (100 μmol/L) produced complete relaxation of partially contracted anococcygeus muscles, but the tone recovered after the ethacrynic acid was washed out. Following exposure to ethacrynic acid, the relaxant responses to NO, SNP, GTN and nitrergic nerve stimulation were abolished or markedly reduced; however, the response to papaverine was only slightly reduced.

3. The presence of 3 mmol/L l‐cysteine during the period of exposure to ethacrynic acid prevented the inhibition of the relaxing effects of SNP, GTN and nitrergic nerve stimulation almost completely, but did not affect the slight reduction in responses to papaverine.

4. The addition of l‐cysteine (3 mmol/L) after incubation with ethacrynic acid did not significantly affect the inhibited responses to SNP and GTN; however, the inhibited responses to nitrergic nerve stimulation were slightly but significantly increased.

5. The results suggest that endogenous sulphydryl groups are required for the actions of NO, NO‐donating drugs and the nitrergic transmitter in the rat anococcygeus muscle and possibly for the synthesis or release of the nitrergic transmitter.
INTERACTIONS BETWEEN THE CIRCULATORY EFFECTS OF CENTRAL HYPOVOLAEMIA AND ARTERIAL HYPOXIA IN CONSCIOUS RABBITS
Authors: Blake Duncan W. , Evans Roger G. , Ludbrook John , Petring Oscar U.
Published: June 2007

1. Eight conscious rabbits were repeatedly subjected to progressive reduction in central blood volume by gradually inflating a thoracic inferior vena caval‐cuff so cardiac index (CI) fell at a constant 8.5% of baseline/min.

2. Caval‐cuff inflations were performed after 10 min exposure to 100, 21, 12–14 and 8–10% O2, with and without the addition of 3–4% CO2, in randomized order.

3. The haemodynamic response to progressive reduction in central blood volume was biphasic. In Phase I, systemic vascular conductance index (SVCI) fell linearly, supporting mean arterial pressure (MAP). When CI had fallen to a critical level, Phase II occurred in which SVCI rose abruptly, MAP plummeted and respiratory drive progressively increased.

4. During Phase I, there were independent linear relationships between Pao2 (but not Pao2) and the rates at which SVCI and MAP changed during the progressive fall of CI. The higher the level of Pao2, the greater was the rate of fall of SVCI and the less the rate of fall of MAP.

5. There was an inverted U‐shaped effect of Pao2, on the level of CI at which Phase II occurred: (a) during hyperoxia (100% O2), Phase II occurred later than during normoxia (21% O2); and (b) across the normoxic and hypoxic gas mixtures (21–8% O2, with and without added CO2), there was an independent linear relationship between Pao2 (but not Pao2 or Pao2×Pao2) and the level of CI at which Phase II occurred. That is, the lower the level of Pao2, the later was the onset of Phase II. This interaction is best explained by an increased level of central sympathetic vasoconstrictor drive during hypoxia.
CILIARY BEAT FREQUENCY AT SIX LEVELS OF THE RABBIT AND RAT RESPIRATORY TRACT IN COW, DOG, GUINEA‐PIG, PIG
Authors: Joki Susanna , Saano Veijo
Published: June 2007

1. The ciliary beat frequency (CBF) of six animal species from six regions of the respiratory tract were measured: inferior turbinate, nasopharynx, the upper part of trachea from first to second cartilage, the lower part of trachea, main bronchus and subsegmental bronchi. Cow, pig, dog, rabbit, guinea‐pig and rat were studied.

2. There were no significant differences in the CBF values between cow, pig and dog, and the ciliary activity was essentially the same (11.3‐16.9 Hz) in all parts of the respiratory tract.

3. In the rat, the CBF was slower, especially in subsegmental bronchi (6.8 Hz).

4. In general, CBF was higher in upper than lower airways, with the exception of guinea‐pig.

5. Signal quality was the highest in guinea‐pig tissue, whereas rat tissue produced the signal with the widest variation in CBF and the highest proportion of distorted waveforms.

6. Therefore, for studying drug effects on ciliary activity, guinea‐pig seems to be a more suitable animal than the more commonly used rabbit or rat. In drug comparisons, the same part of the respiratory tract and the same animal species should be used.
LOCAL NEURAL CONTROL OF INTESTINAL MOTILITY: NERVE CIRCUITS DEDUCED FOR THE GUINEA‐PIG SMALL INTESTINE
Authors: Bornstein J. C.
Published: June 2007

1. Propulsion of digesta along the intestine appears to occur by the action of a series of local reflexes which cause contraction oral to the digesta and relaxation of circular muscle on the anal side.

2. There is now substantial evidence available about the identities of the enteric neurons that mediate these reflexes.

3. The motor neurons and interneurons of the reflex pathways lie within the myenteric plexus. These neurons can be classified electrophysiologically as S‐neurons and have distinctive projections and neurochemistries.

4. The sensory neurons may lie in the myenteric plexus, but there is some evidence for sensory neurons in the submucous plexus. A contribution from extrinsic sensory neurons to local motility reflexes cannot be ruled out. Intrinsic sensory neurons are probably AH‐neurons and are large multi‐axonal cells.
ALINIDINE PREVENTS HYPOPERFUSION‐INDUCED TRANSMURAL FLOW REDISTRIBUTION IN ISOLATED PACED RAT HEARTS
Authors: Weihs H. , Mutschled E. , Walland A.
Published: June 2007

1. The effect of alinidine on transmural flow redistribution during hypoperfusion was studied in the isolated rat heart.

2. Low flow perfusion of paced (5 Hz) rat Langendorff preparations with Tyrode's solution for 60 min resulted in loss of left ventricular pressure amplitude and contracture.

3. In the presence of 45.6 μmol/L alinidine in the hypoperfusion medium contractility was maintained and contracture was missing.

4. Myocardial sphere densities were assessed by infusion of fluorescent microspheres after 60 min of hypoperfusion. Histomorphometric evaluation of the left ventricular wall indicated marked redistribution of myocardial flow to the epicardium. Endolepicardial quotients of sphere densities were significantly greater in alinidine‐treated hearts.

5. Perfusion of hearts with 45.6 μmol/L alinidine for 30 min at a pressure of 80 cmH2O decreased coronary flow and contractility, but did not change the transmural quotient of sphere densities.

6. These results show that in isolated rat hearts with a ventricular wall of only 3–4 mm thickness severe hypoperfusion induces a shift in transmural flow distribution which is prevented by alinidine.
ANTI‐OBESITY AND ANTI‐DIABETIC EFFECTS OF CARTEOLOL IN NON‐INSULIN‐DEPENDENT DIABETIC MICE
Authors: Takahashi Hakuo , Nakano Koji , Yasuda Tomoko , Komiyama Yutaka , Murakami Takashi , Nishimura Masato , Nakanishi Tadashi , Sakamoto Masanori , Nanbu Akira , Yoshimura Manabu
Published: June 2007

1. When carteolol, a β‐adrenergic blocker, was administered to KK‐Ay/Ta Jcl mice that are obese and develop spontaneously non‐insulin dependent diabetes, their increase in bodyweight was arrested from the age of 16 weeks. Since their intake of food and water was not influenced by carteolol treatment, compared with the control KK‐Ay/Ta Jcl mice, abolition of the weight gain might be attributed to increased energy metabolism.

2. Non‐fasting serum glucose levels in carteolol‐treated mice at the age of 17 weeks were within normal range (118±4 vs 186±12 mg/dL). An intraperitoneal glucose‐tolerance test revealed that the carteolol treatment markedly restored glucose metabolism; fasting plasma glucose (88±6 mg/dL) was within normal range, and immunoreactive insulin (IRI; 5.8±0.8 vs 33.3 ± 10.5 ng/mL) and plasma glucose levels at 60 min post glucose (361±44 vs 541 ±32 mg/dL) were significantly lower in carteolol‐treated mice than those in the control group at the age of 20 weeks.

3. From these findings, carteolol is considered to have little effect on the growth of mice but to correct the obesity that develops after age 16 weeks, when their growth terminates. In addition, the normalization of blood glucose and marked decrease in IRI levels suggests that carteolol improves glucose tolerance by increasing the insulin sensitivity.

4. Since brown adipose tissue (BAT) is closely associated with thermogenesis and energy consumption, we tested whether carteolol may affect BAT, When the regional blood flow was measured by radioactive microspheres in rats, blood flow in BAT and white adipose tissue was markedly increased by carteolol.

5. These findings indicate that carteolol blocks β1‐ and β2‐adrenoceptors, but may stimulate β‐receptors particularly in the adipose tissue to promote lipolysis and thermogenesis, and to consume excess energy in mice. Thus, carteolol does not influence mouse growth, but may prevent obesity leading to increases in insulin sensitivity.
POSSIBLE MECHANISMS INVOLVED IN THE NATRIURETIC RESPONSE TO ATRIAL NATRIURETIC FACTOR (ANF) AND PROANF 31–67 IN THE RAT
Authors: Dietz John R. , Vesely David L. , Nazian Stanley J.
Published: June 2007

1. The present study was conducted to compare the mechanisms involved in the natriuretic response to atrial natriuretic factor (ANF) and pro ANF 31–67. The peptides were infused intravenously into anaesthetized rats at 10 pmol/min for 40 min.

2. Only ANF produced a significant decrease in arterial pressure; the maximum decrease was 11 mmHg (P<0.05).

3. Both peptides produced significant increases in sodium excretion (P<0.05) but only ANF increased the cyclic GMP (cGMP) excretion rate (P<0.01) and neither peptide had a significant effect on plasma renin activity or glomerular filtration rate (GFR). Pro ANF 31–67 did not increase the plasma levels of ANF.

4. These results demonstrate that both ANF and proANF 31–67 have natriuretic effects via a tubular mechanism and suggest that the natriuretic effects of ANF are mediated by cGMP while the effects of pro ANF 31–67 are mediated by a different mechanism, not involving changes in cGMP excretion, changes in GFR or a reduction in renin secretion.
DEXTROSE‐, ADENOSINE‐ AND MAGNESIUM‐INDUCED PROTECTIVE ACTIONS DURING ANOXIA AND REPERFUSION IN CANINE PURKINJE TISSUE
Authors: Bhattacharyya M. L. , Sarker S. , Seth K.
Published: June 2007

1. The effects of dextrose, magnesium (Mg) and adenosine on membrane potential and force of contraction were studied in driven and overdriven canine cardiac Purkinje tissue.

2. Dextrose (50 mmol/L) and adenosine (4–6 mmol/L) both showed protective action (the latter to a lesser extent) against simulated anoxia and reperfusion‐ induced arrhythmias, increased force of contraction transiently on reperfusion, and the former sustained the increase in force to a lower level as long as it was in the superfusing solution.

3. Dextrose (50 mmol/L) and Mg (5 mmol/L) restored overdrive‐ induced hyperpolarization during simulated anoxia. Adenosine was largely ineffective.

4. It was concluded that dextrose and adenosine (to a lesser extent) protect against arrhythmias by replenishing the critical intracellular pool of ATP which controls membrane transport of electrolytes such as K and Ca. Restoration of Na‐K ATPase activity alone (as in the case of high Mg concentrations) is not sufficient to prevent arrhythmias.
CHARACTERIZATION OF BINDING SITES FOR [3H]‐IDAZOXAN, [3H]‐P‐AMINOCLONIDINE AND [3H]‐RAUWOLSCINE IN THE KIDNEY OF THE DOG
Authors: Evans Roger G. , Haynes John M.
Published: June 2007

1. We characterized the binding of [3H]‐rauwolscine, [3H]‐p‐aminoclonidine and [3H]‐idazoxan in a dog kidney membrane preparation. Our aim was to determine the pharmacological nature of the α2‐adrenoceptor‐ and imidazoline‐preferring binding sites in this organ.

2. [3H]‐Rauwolscine bound to an apparent single site with an affinity (KD) of 2.2 nmol/ L and a maximum density (Bmax) of 58.5 fmol/mg protein, when 10 μmol/L idazoxan defined non‐specific binding. However displacement studies demonstrated that a number of compounds, including prazosin, inhibited [3H]‐rauwolscine binding in a complex manner consistent with displacement from two distinct binding sites. The majority (69%) of the [3H]‐rauwolscine binding sites had a relatively low affinity for prazosin (KI= 398 nmol/L), while the remainder had a relatively high affinity for prazosin (KI= 7.9 nmol/ L).

3. [3H]‐p‐Aminoclonidine bound to an apparent single site (KD= 5.2 nmol/L; Bmax= 72.4 fmol/mg protein), when 10 μmol/L phentolamine defined non‐specific binding. When 1 μmol/L of the potent and selective α2‐adrenoceptor antagonist 2‐methoxyidazoxan was included in the incubate, no specific binding was detected. We therefore conclude that under the conditions of this experiment [3H]‐p‐aminoclonidine binds only to α2‐adrenoceptors in the dog kidney.

4. [3H]‐Idazoxan bound to two sites, with a higher (KD= 0.95 nmol/L; Bmax= 43.9 fmol/mg protein) and lower (KD= 9.1 nmol/L; Bmax= 93.8 fmol/mg protein) affinity, respectively, when 1 mmol/L phentolamine defined non‐specific binding. When 10 μmol/ L GTPγS was included in the incubate, the low affinity site was unaffected but the maximum binding at the higher affinity site was reduced by 79%. 2‐Methoxyidazoxan displaced [3H]‐idazoxan in a monophasic manner and with low potency (IG50=11.5 μmol/L). Yohimbine, efaroxan, clonidine, rilmenidine, guanabenz and idazoxan itself displaced [3H]‐idazoxan in a complex manner; the slope of the displacement curves being less than unity.

5. We conclude that the dog kidney contains a heterogeneous population of α2‐adrenoceptors that can be labelled either with [3H]‐rauwolscine or [3H]‐p‐aminoclonidine. The dog kidney also contains a heterogeneous population of non‐adrenoceptor imidazoline‐preferring binding sites of the I2‐subtype, that can be labelled with [3H]‐idazoxan. The binding site for which [3H]‐idazoxan has the highest affinity appears to be coupled to a guanine nucleotide binding regulatory protein.
CLEARANCE OF CHYLOMICRON‐LIKE LIPID EMULSIONS IS INCREASED IN NORMAL RABBITS BUT NOT IN HETEROZYGOUS WATANABE HERITABLE HYPERLIPIDAEMIC RABBITS FOLLOWING TREATMENT WITH CHOLESTYRAMINE OR PRAVASTATIN
Authors: Mamo J. C. L. , Bowler A. , Redgrave T. G. , Elsegood C. L.
Published: June 2007

1. Cholestyramine and pravastatin are two potent hypocholesterolaemic drugs which lower plasma cholesterol by increasing the clearance of low density lipoproteins by high affinity uptake mechanisms.

2. We gave heterozygous Watanabe heritable hyperlipidaemic rabbits (hz‐WHHL) cholestyramine and/or pravastatin for a two week period to try and ameliorate slow clearance of chylomicron remnants, which occurs because of reduced expression of the apolipoprotein B100/E receptor.

3. In hz‐WHHL rabbits the clearance of chylomicron‐like lipid emulsions, traced by the decrease in plasma cholesteryl oleate radioactivity was not improved following treatment with either of the cholesterol lowering drugs.

4. In contrast, control rabbits had significantly less chylomicron‐like emulsion cholesteryl‐ester radioactivity remaining at each time of blood sampling.

5. Similarly, the clearance of chylomicron‐like emulsion triolein was enhanced in normal rabbits receiving cholestyramine or pravastatin, whereas there was no detectable increase in clearance in hz‐WHHL rabbits.

6. Combined treatment with cholestyramine and pravastatin increased the rate of receptor‐mediated uptake in vivo in control rabbits but not in hz‐WHHL rabbits.

7. The plasma lipid profiles of control and hz‐WHHL rabbits parallelled the patterns of chylomicron‐like emulsion clearance. Moderate hypertriglyceridaemia was identified in hz‐WHHL rabbits compared to controls and there was no change in plasma triglyceride or cholesterol following drug therapy. In contrast, control rabbits had decreased plasma lipids following cholestyramine or pravastatin treatment.

8. It appears that therapy with lipid lowering drugs increased chylomicron remnant clearance in control rabbits by up‐regulation of the apolipoprotein BIOO/E receptor. In contrast, in hz‐WHHL rabbits receptor activity did not appear to be increased sufficiently to ameliorate defective remnant clearance. We have suggested that a critical receptor density is required for efficient remnant clearance.
DISEASE‐INDUCED CHANGES IN α‐ADRENOCEPTOR‐MEDIATED CARDIAC AND VASCULAR RESPONSES IN RATS
Authors: Brown Lindsay , Amos Gregory , Miller Brendan
Published: June 2007

1. The physiological relevance of cardiac and vascular α‐adrenoceptors may increase in disease states in which β‐adrenoceptors are altered. To test this, positive inotropic and vasoconstrictor responses to phenylephrine were measured in isolated tissues from rats with experimentally‐induced hyperthyroidism, hypothyroidism and diabetes as well as in genetically spontaneous hypertensive rats (SHR).

2. In left atria, positive inotropic responses to phenylephrine were increased in hypothyroid and diabetic rats and abolished in hyperthyroid and SHR.

3. In contrast, phenylephrine produced increased positive inotropy in left ventricular papillary muscles from hyperthyroid rats, increased potency in diabetic rats and negative inotropic responses in hypothyroid rats.

4. The potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was increased in hyperthyroid and SHR and decreased in hypothyroid rats.

5. Thus, disease states which alter β‐adrenoceptor responsiveness can independently regulate atrial, ventricular and vascular responses to the α1‐adrenoceptor agonist, phenylephrine. Therefore, these disease states may alter the physiological control of the cardiovascular system by noradrenaline and adrenaline as well as the responsiveness in disease states to therapeutic agents acting via α‐adrenoceptors.
PHARMACOLOGICAL PROPERTIES OF THE NATURAL MARINE PRODUCT FUROSPONGIN‐1
Authors: Anderson Andrew P. , Beveridge Andrew A. , Capon Robert
Published: June 2007

1. The natural marine product, furospongin‐1 (6, 12 and 24.5 μmol/L) significantly inhibited contractions of segments of guinea‐pig ileum induced by submaximal concentrations (0.1 μmol/L) of acetylcholine (ACh) and histamine. Furospongin‐1 (24.5 and 36.7 μmol/L) reduced both the phasic and tonic components of a contraction induced by 30 mmol/L K+ solution in the absence and presence of atropine (1 μmol/L), mepyramine (1 μmol/L) and phentolamine (1 μmol/L). Furospongin‐1 also decreased basal tension and the amplitude of spontaneous phasic contractions of guinea‐pig ileum.

2. The mitochondrial ATP synthase inhibitor oligomycin (0.3, 1 and 3 μmol/ L) had a similar concentration‐dependent action, reducing basal activity and contractions evoked by histamine and ACh. Oligomycin also reduced both the phasic and tonic components of a contraction induced by 30 mmol/L K+ solution in the absence and presence of atropine (1 μmol/L), mepyramine (1 μmol/L) and phentolamine (1 μmol/L).

3. Furospongin‐l (6 and 37.6 μmol/L) and oligomycin (3 μmol/L) had no effect on contractions of chemically skinned guinea‐pig ileum longitudinal muscle segments. In this same tissue, furospongin‐1 (6, 12 and 24.5 μmol/L) and oligomycin (0.3, 1 and 3 μmol/L) concentration‐dependently reduced tissue levels of ATP.

4. In lyzed bovine mitochondria, oligomycin (0.1, 0.3, 1 and 3 μmol/L) inhibited conversion of ATP to ADP whilst furospongin‐1 (6, 12 and 24.5 μmol/L) and carbonyl cyanide m‐chlorophenylhydrazone (0.5 mmol/L) had no significant effect on ATP breakdown.

5. Furospongin‐1 (12 and 24.5 μmol/L) and oligomycin (3 μmol/L) had no effect on State 4 mitochondrial respiration of whole bovine mitochondria, but converted State 3 back to State 4 respiration. Carbonyl cyanide m‐chlorophenyl‐hydrazone (0.5 mmol/L) increased oxygen consumption in both situations.

6. These results suggest that furospongin‐1 may inhibit the activity of inner mitochondrial membrane ADP‐ATP translocases or other membrane transporters to inhibit ATP synthesis.
THE DIFFERENCE IN NIFEDIPINE SENSITIVITY BETWEEN HYPERTENSIVE AND NORMOTENSIVE RAT AORTAE IS DEPENDENT ON AGE
Authors: Jiang Guang‐Chi , Iwanov Victor , Moulds Robert F. W.
Published: June 2007

1. In order to investigate further whether the increased sensitivity to inhibition by nifedipine of the responses to nor‐adrenaline of aortae from spontaneously hypertensive stroke‐prone (SHRSP) rats is related to the development of the hypertension, we have compared the sensitivity to noradren‐aline, potassium chloride (KCl) and nifedipine of aortae from SHRSP and control (Wistar‐Kyoto) WKY rats of different age groups (young: 3–5 weeks, and adult: 13–16 weeks).

2. The sensitivity to KCl was found to be less in the aortae from the adult WKY group than in any of the other three groups. Responses to noradrenaline of the adult WKY aortae were also less sensitive to inhibition by nifedipine in comparison to each of the other three groups.

3. The changes in sensitivity were not due to the changes in the populations of α1‐adrenoceptor subtypes as responses of the adult SHRSP aortae to noradrenaline were more sensitive to nifedipine in the presence of either the α1‐adrenoceptor subtype antagonists chloroethylclonidine or WB 4101 than were those of the adult WKY aortae, but aortae from the young SHRSP were not.

4. These results suggest that, rather than the SHRSP aorta becoming more sensitive to nifedipine and potassium depolarization as hypertension develops, it is the WKY aorta that becomes more resistant as it matures.
MOLECULAR BIOLOGY AND BIOCHEMISTRY OF NATRIURETIC PEPTIDE FAMILY
Authors: Ogawa Yoshihiro , Itoh Hiroshi , Nakao Kazuwa
Published: June 2007

The natriuretic peptide family consists of three endogenous ligands; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C‐type natriuretic peptide (CNP), and is involved in the regulation of cardiovascular homeostasis. Both ANP and BNP act mainly as cardiac hormones and are produced predominantly by the atrium and ventricle, respectively. Expression of the BNP and ANP genes is greatly augmented in patients with congestive heart failure and animal models of ventricular hypertrophy or cardiomyopathy. In the heart, the BNP gene expression is regulated differently from the ANP gene expression both at transcriptional and post‐transcriptional levels. Transgenic technology has provided the direct evidence that BNP as well as ANP is involved in the chronic blood pressure control. Contrasting with ANP and BNP, CNP does not act as a cardiac hormone but as a neuropeptide or an endothelium‐derived autocrine/paracrine regulator. Endothelial production of CNP is remarkably augmented by various cytokines and growth factors such as transforming growth factor‐β and tumour necrosis factor‐α, suggesting the pathophysiological significance of CNP in the process of various vascular disorders. Chromosomal mapping of natriuretic peptides has revealed that the CNP gene is localized on mouse chromosome 1, while ANP and BNP are tightly linked on mouse chromosome 4, suggesting that CNP, a local regulator, is functionally and evolutionarily distinct from ANP and BNP, both of which are cardiac hormones. Understanding the molecular biology and biochemistry of the natriuretic peptide family will lead to the better understanding of its physiological and pathophysiological implication, and the clinical application in cardiorenal regulation.
CARDIOVASCULAR ACTIONS OF INSULIN: ARE THEY IMPORTANT IN LONG‐TERM BLOOD PRESSURE REGULATION?
Authors: Hall John E. , Brands Michael W. , Zappe Dion H. , Alonso‐Galicia Magdalena
Published: June 2007

1. In recent years, there has been considerable interest in the possibility that insulin may have important cardiovascular as well as metabolic actions. Perhaps the best documented cardiovascular effect of insulin is to cause peripheral vasodilation, especially in skeletal muscle. Hyperinsulinaemia also stimulates sympathetic activity and causes antinatriuresis, but these effects may be linked, at least in part, to the metabolic actions of insulin that elicit peripheral vasodilation and a tendency toward hypotension. Normal, fasting levels of insulin appear to have very little influence on peripheral vascular resistance, sympathetic activity or renal sodium excretion.

2. Decreased sensitivity of the peripheral tissues to the metabolic effects of insulin and compensatory hyperinsulinaemia have been postulated to play key roles in the pathophysiology of diseases such as hypertension and atherosclerosis. Although impaired insulin action (insulin resistance) and hyperinsulinaemia often accompany essential hypertension, especially when associated with obesity, there is currently little direct evidence for a cause and effect relationship between insulin resistance, hyperinsulinaemia and increased arterial pressure. Chronic increases in plasma insulin levels in dogs and humans have not been shown to cause hypertension, although hyperinsulinaemia raises blood pressure in rats.

3. Further research is needed to determine whether there are pathophysiological conditions or genetic factors that may predispose humans to a hypertensive effect of hyperinsulinaemia and/or insulin resistance.
ELECTROPHYSIOLOGICAL PROPERTIES OF THE RAT MIDDLE CEREBRAL ARTERY AT DIFFERENT LEVELS OF PASSIVE WALL TENSION
Authors: McPherson Grant A. , Keily Simon G.
Published: June 2007

1. Simultaneous measurements of intracellular membrane potential and myogenic tone of proximal segments of the rat middle cerebral artery, mounted in a small vessel myograph, were made at two levels of passive wall tension.

2. At low levels of passive tension (less than 0.25mN/mm) vessels had a resting membrane potential of approximately ‐65mV. Addition of KCl (5–60 mmol/L), BaCl2 (0.01–3 mmol/L) or tetraethylammonium (TEA; 0.1–3 mmol/L) resulted in a concentration‐dependent depolarization, to approximately—40 mV, generally associated with a contractile response. After the application of high levels of passive tension (to approximately 2mN/mm maximum) the resting membrane potential of the smooth muscle cells was—40 to—45 mV. This more positive membrane potential was generally associated with an increase in myogenic tone of the vessel. Under these conditions, addition of 5–20 mmol/L KCl resulted in a strong hyperpolarization of the cell along with a concomitant decrease in myogenic tone of the artery. The hyperpolarization and vasorelaxation induced by KCl (5–20 mmol/L) were blocked by BaCl2 (0.5–1 mmol/L).

3. While the addition of ryanodine (10 μmol/L) to vessels under low tension had no effect, when added to a vessel under high tension, this agent caused a rhythmic oscillation in membrane potential. This oscillation was augmented by BaCl2 (1mmol/L) and inhibited by nifedipine (10nmol/L) and 4‐aminopyridine (1 mmol/L).

4. This study suggests that the electrophysiological and mechanical properties of the isolated rat middle cerebral artery depend on the passive resting conditions under which the vessel is studied. The depolarization of membrane potential observed with increased passive tension appears to result from the closure of an inward rectifying K+ channel. These results indicate that the inward rectifying K+ channel plays an important role in regulating vascular reactivity due to its functional dependence on the mechanical status of the blood vessel.
EFFECTS OF DIETARY FIBRE ON DIMETHYLHYDRAZINE‐INDUCED CHANGES IN PROSTANOID CONCENTRATIONS IN RAT COLONIC MUCOSA
Authors: Kanamori Shin‐ichi , Sugiyama Satoru , Goto Hidemi , Hayakawa Tetsuo , Shimomura Yoshiharu , Ozawa Takayuki
Published: June 2007

1. This study was designed to elucidate the effects of guar gum, a dietary fibre, on changes in prostanoid contents induced by 1,2‐dimethylhydrazine, a carcinogenic agent, in rat colonic mucosa.

2. Prostanoid contents were determined using high performance liquid chromatography; five prostanoids, namely 6‐keto‐prostaglandin F1α, prostaglandin F2α, prostaglandin E2, prostaglandin D2 and thromboxane B2, were detected.

3. Four subcutaneous injections of dimethylhydrazine, 60 mg/kg every 6 days, increased the mucosal concentrations of prostaglandin E2 and thromboxane B2 by approximately 50%. Other prostanoids did not change significantly throughout the experiments.

4. In rats treated with dimethylhydrazine and a fibre diet a significant increase in thromboxane B2 content was not observed, although a significant increase in prostaglandin E2 content was observed. These effects were observed in rats fed with fibre diet over 20 days but not observed in rats fed with fibre diet over 10 days.

5. From these results and the report that aspirin use at low doses is effective in the reduction of the risk of fatal colonic cancer, inhibiting thromboxane B2 synthesis by fibre diet might he involved in the protective effect against the occurrence of colonic cancer.
EFFECTS OF ENDOTHELIN‐1 ON THE CONTRACTILITY OF CARDIOMYOCYTES FROM THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Delbridge Leanne M. , Morgan Trefor O. , Harris Peter J.
Published: June 2007

1. Disturbances in cardiovascular responsiveness to endogenous endothelin‐1 (ET‐1) may play a significant role in the pathogenesis of essential hypertension. In this study the inotropic responses of cardiomyocytes derived from normotensive Wistar‐Kyoto (WKY) and spontaneously hypertensive rat (SHR) strains to ET‐1 (10‐11‐10‐8 mol/L) were characterized. Isotonic contraction cycles of ventricular cardiomyocytes isolated from age‐matched (11 week) WKY and SHR rats were recorded using a rapid digital imaging technique and evaluated by computation of a range of normalized parameters.

2. The maximum effect of ET‐1, eliciting a 60–70% increase in myocyte shortening after 3 min, was observed at 10‐9 mol/L in both strains, and was associated with elevations in the rate of shortening and lengthening, abbreviated latency, contractile cycle prolongation and delayed time to peak shortening.

3. No evidence for a significant strain dependent difference in the relative responsiveness to ET‐1 was detected. This finding indicates that altered sensitivity to ET‐1 is unlikely to be a major factor underlying the development of hypertension in this model.

4. The distinct nature of the alterations in contractile parameters produced by ET‐1 compared with angiotensin II (AII) suggests that the prevailing cellular mechanisms of action of these peptides are different and that ET‐1 is not a paracrine or autocrine inotropic intermediate for AII
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: OPPOSING ROLES FOR DOPAMINE AND SEROTONIN AT PRESYNAPTIC RECEPTORS IN THE VENTRAL TEGMENTAL AREA
Authors: Cameron D. L. , Williams J. T.
Published: June 2007

1. Dopamine D1 and SHT1d receptors are found on the terminals of afferent GABA neurons that synapse on the ventral tegmental area (VTA) dopamine neurons. The role of these receptors in the actions of cocaine was investigated using intracellular recordings in a brain slice preparation. Synaptic potentials were generated in the slice and GABA‐mediated inhibitory post‐synaptic potentials (IPSP) were identified.

2. Stimulation of dopamine D1 receptors selectively enhanced the GABAb IPSP, and this effect was blocked by D1 antagonists. The magnitude of the IPSP was decreased when D1 antagonists were applied in isolation, suggesting tonic D1 receptor stimulation via dendritically released dopamine.

3. Cocaine had an opposite effect and selectively decreased the magnitude of the GABAb IPSP. This action was mimicked by 5HT and the SHT1d agonist sumatriptan, and attenuated by the 5HTI1D/2c antagonist, metergoline. The action of cocaine was also mimicked by the 5HT‐releasing agent, fenfluramine, and blocked by pre‐incubation of the slice with the 5HT‐depleting agent, para‐chloroamphetamine.

4. The results of this study suggest that dopamine and 5HT have opposing roles in modulating GABA input into VTA dopamine neurons. The actions of cocaine on this interplay may have implications for understanding its addictive properties.
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: FREE RADICAL TOXICOLOGY AND ANTIOXIDANT DEFENCE
Authors: Winterbourn Christine C.
Published: June 2007

1. A large number of compounds that have toxic effects can be metabolized to free radicals and secondary reactive oxygen species. These may be directly damaging or may affect cell function by altering regulatory mechanisms through changing redox status.

2. Protection is provided by an integrated system of anti‐oxidant defences. This includes reduced glutathione, one of the functions of which is to scavenge free radicals. It acts by channelling radicals to superoxide so that the one enzyme, superoxide dismutase, has a major control over radical reactions in the cell.
CHANGES IN INTRA‐ AND EXTRACRANIAL TISSUE BLOOD FLOW UPON STIMULATION OF A RETICULAR AREA DORSAL TO THE FACIAL NUCLEUS IN CATS
Authors: Kuo Jon‐Son , Chyi Theresa , Yang May C. M. , Chai Chok‐Yung
Published: June 2007

1. A small area in the dorsal part of the lateral tegmental field specifically responsible for the increase of blood flow in the common carotid artery (CCA) without accompanying change in the resting blood pressure was first identified in our laboratory. Since the area is located just dorsal to the facial nucleus, we named it the dorsal facial area (DFA; Kuo et al. 1987).

2. The purpose of this study was to clarify whether an increase of blood flow in intra‐ and/or extracranial tissues was responsible for the increase in CCA blood flow upon DFA stimulation, and to determine the role of cholinergic transmission in this response.

3. In 20 cats under chloralose and urethane anaesthesia, microsphere reference flow technique was used to measure the regional blood flow of intra‐ and extracranial tissues.

4. Electrical stimulation of the DFA appeared to increase the regional blood flow of both cerebral hemispheres (intra‐cranial tissues) and to increase predominantly the regional blood flow of extracranial tissues on the side ipsilateral to stimulation. Increases in the regional blood flow of intracranial tissues were enhanced after i.v. administration of atropine but reduced with physostigmine. In contrast, increases in the regional blood flow of extracranial tissues were reduced after i.v. atropine but enhanced after physostigmine.

5. These findings suggest that DFA stimulation may promote the release of ACh in intra‐ and extracranial vessels. The muscarinic action may restrict the DFA‐induced increase in blood flow of intracranial tissues, but enhance that of extracranial tissues.
ATRIAL NATRIURETIC PEPTIDE FRAGMENTS IN DOGS WITH EXPERIMENTAL HEART FAILURE
Authors: Habibullah Ahmed A. , Villarreal Daniel , Freeman Ronald H. , Dietz John R. , Vesley David L. , Simmons John C.
Published: June 2007

1. This study in the canine arteriovenous (AV) fistula model of high‐output heart failure (HOHF) evaluated the chronic temporal changes in plasma ANF and pro ANF 31–67 and their relationship to body‐fluid balance and the renin‐aldosterone axis. In addition, the haemodynamic, hormonal and renal excretory effects of synthetic pro ANF 31–67 infusions were examined in normal and AV fistula dogs with compensated HOHF.

2. Following the construction of the AV fistula, the dogs exhibited chronic parallel elevations in right atrial pressure and the plasma concentrations of ANF and pro ANF 31–67. The gradual increases in the two peptides were associated with a gradual decrease in plasma renin activity and the re‐establishment of sodium balance.

3. In normal and compensated AV fistula dogs, synthetic pro ANF 31–67 produced similar significant reductions in arterial blood pressure, right atrial pressure and elevations in urinary sodium excretion. These effects were not associated with increases in plasma or urinary cyclic GMP (cGMP).

4. These results suggest that the elevation in the endogenous circulating levels of pro ANF 31–67 in the AV fistula dogs may represent one chronic adaptive mechanism to achieve body fluid homeostasis. Furthermore, via potentially different mechanisms of action, ANF and pro ANF 31–67 may coordinate and contribute to the regulation of haemodynamic and renal function during physiological and pathophysiological situations.
CONTROL OF INTRAVASCULAR VOLUME DURING PREGNANCY
Authors: Kaufman Susan
Published: June 2007

1. We wished to determine whether, during pregnancy, there is reduced renal response to atrial distension, whether secretion of atrial natriuretic factor (ANF) is suppressed and whether neural input from the atrial volume receptors to the central nervous system is altered.

2. Conscious, chronically instrumented female rats were used. Atrial distension was achieved by implanting small balloons positioned at the superior vena caval/right atrial junction; inflation of the balloon did not impede blood flow through the heart.

3. In virgin rats, atrial stretch caused increased urine volume, urine sodium and potassium output and decreased free water clearance. These responses were abolished during pregnancy.

4. In response to atrial stretch, plasma ANF levels increased significantly in virgin rats. No such secretory response was observed in the pregnant animals.

5. Distension of isolated atria derived from unmated and 7 day pregnant rats resulted in an increase in secretion of ANF into the perfusate. Atria from 14 and 21 day pregnant rats were unresponsive to distension.

6. Pretreatment with oestradiol (50 μg daily for 10 days) caused plasma ANF levels and ANF secretion by isolated perfused atria to increase. By contrast, testosterone pretreatment (15 mg twice weekly for 2 weeks) abolished stretch induced secretion of ANF by isolated atria.

7. C‐fos activity in the paraventricular nucleus of virgin rats increased in response to atrial distension. This response was reduced in the 7 day pregnant rats and abolished at 21 days.

8. We conclude that there is attenuation of both hormonal and neural responses to atrial distension in the pregnant animal. This allows blood volume to increase without eliciting homeostatic mechanisms to eliminate the extra fluid.
ALCOHOL, HYPERTENSION, CORONARY DISEASE AND STROKE
Authors: Lip Gregory Y. H. , Beevers D. Gareth
Published: June 2007

1. The association between alcohol and hypertension has been recognized for several years.

2. However, it remains a paradox that if alcohol does cause hypertension there is little convincing evidence that alcohol is related to the cardiovascular complications of hypertension such as strokes and heart attacks. The relationship between alcohol and strokes remains inconclusive and there is evidence that moderate alcohol consumption may be protective against heart attacks.

3. It is possible, therefore, that alcohol does not so much cause hypertension, but rather a rapidly reversible rise in blood pressure which does not cause cardiovascular damage. When managing hypertensive patients, however, relevant counselling can bring about a useful fall in blood pressure.
CAN WE RECOMMEND FISH OIL FOR HYPERTENSION?
Authors: Howe Peter R. C.
Published: June 2007

1. The ability of the n‐3 fatty acids in fish oil to lower blood pressure has been established. Dietary fish oil supplementation is effective in mild hypertension and, in certain cases, as an adjunct therapy in drug‐treated hypertension. Efficacy may be enhanced by restricting sodium intake.

2. The overall benefit of fish oil in hypertension, however, has not yet been fully evaluated. We still need further information on the relative efficacy of individual omega‐3 fatty acids and on additional cardiovascular benefits and possible disadvantages of increasing their consumption.