bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECTS OF CILAZAPRIL ON THE STRUCTURE OF MESENTERIC RESISTANCE ARTERIES OF NEW ZEALAND GENETICALLY HYPERTENSIVE AND NORMOTENSIVE CONTROL RATS
Authors: Ledingham J. M. , Phelan E. L. , Millar J. A.
Published: June 2007

1. New Zealand genetically hypertensive (GH) rats and their normotensive controls (N) rats between the ages of 10 and 16 weeks were treated with cilazapril in the diet for 6 weeks.

2. Systolic blood pressure (SBP; tail‐cuff) was measured weekly and intra‐arterial blood pressure (BP) was measured at the end of the treatment period.

3. The effect of cilazapril on the structure of mesenteric resistance arteries (MRA) was evaluated by both stereological and myographic techniques.

4. Cilazapril lowered SBP significantly throughout the treatment period (16 weeks; GH with cilazapril 135 ± 5 vs GH 216 ± 9 mmHg, P < 0.001; N cilazapril 91 ± 6 vs N 137 ± 3 mmHg, P < 0.001); intra‐arterial BP was also significantly lowered.

5. Bodyweight (BW) of treated GH rats was significantly lower than that of untreated GH at 16 weeks (P < 0.01; t‐test); however, the weight of treated N rats was not significantly affected. Ventricular mass was reduced by cilazapril in GH and N rats (GH 259 ± 10 vs 306 ± 11, P < 0.001; N 171 ± 3 vs 195 ± 4 mg/100g BW, P < 0.001).

6. Lumen volume of MRA was not significantly affected by cilazapril in either strain; media volume was reduced by 14% in both strains and the media/lumen ratio was significantly reduced. Vascular smooth muscle cell density significantly increased in cilazapril‐treated GH rats.
THE DOPAMINE PRODRUG, GLUDOPA, DECREASES BOTH RENAL AND EXTRARENAL NORADRENALINE SPILLOVER IN CONSCIOUS RABBITS
Authors: Wang Zhi‐Qin , Shimizu Kazumasa , Way Diana , Secombe John , McGrath Barry P.
Published: June 2007

1. Renal and total noradrenaline (NA) spillover rates were examined under control conditions and during graded infusions of gludopa (γ‐l‐glutamyl‐l‐dopa) in conscious rabbits.

2. Gludopa infusion at 25 and 100 μg/kg per min did not alter mean arterial pressure (MAP) and heart rate (HR), but had significant dose‐related effects on the renal dopamine (DA) system. At the high dose there were pronounced increases in urinary DA excretion (>6000‐fold) and renal DA content (> 100‐fold); renal NA content doubled.

3. Renal venous DA increased after gludopa infusion, but arterial plasma DA concentrations were not significantly changed. Mean arterial plasma gludopa and l‐dopa concentrations reached 890, 3190 ng/mL and 3, 10 ng/mL at low and high doses, respectively.

4. Gludopa resulted in a pronounced dose‐dependent fall in renal NA spillover, which at 100 μg/kg per min accounted for almost half of the reduction in overall NA spillover rate.

5. The significant falls in renal and extrarenal NA spillover rate during gludopa infusion are consistent with suppression of renal and overall sympathetic activity. Gludopa‐induced inhibition of renal NA spillover is likely to be due to the actions of DA generated in the kidney on presynaptic DA‐2 and α‐2 receptors. A central sympathoinhibitory mechanism may explain the reduced total NA spillover.
VASOPRESSIN COMPENSATES FOR ACUTE LOSS OF SYMPATHETIC PRESSOR TONE IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Jablonskis Lina T. , Howe Peter R. C.
Published: June 2007

1. The aim of this study was to examine the pressor response of vasopressin (AVP) to an acute fall in blood pressure induced by ganglion blockade.

2. Aortic catheters were implanted in spontaneously hypertensive rats (SHR), stroke‐prone SHR (SHRSP), normotensive Wistar‐Kyoto (WKY), black‐hooded Wistar (BHW) and Sprague‐Dawley (SD) rats, aged 5–7 weeks and 7–9 months, for direct measurement of mean arterial pressure (MAP) under conscious, resting conditions. The ganglion blocking agent pentolinium was administered intra‐arterially, followed by an AVP receptor antagonist specific for the pressor effect of AVP. The basal level of MAP attained with each drug was recorded.

3. In the adult SHR and SHRSP with established hypertension, acute ganglion blockade caused MAP to fall to a similar extent as in WKY, suggesting that the level of sympathetic pressor tone was similar in all three strains. Administration of the AVP antagonist alone did not affect resting MAP. During ganglion blockade, however, it caused a further reduction of MAP in WKY, SHR and SHRSP, the magnitude of which was greater in the hypertensive strains. After both drugs, the total fall in MAP and the residual MAP were significantly greater in the hypertensive rats.

4. In young rats, AVP had little effect on MAP, even during ganglion blockade. The residual level of MAP after both drugs was greater in the hypertensive strains.

5. The extent to which AVP can compensate for an acute fall in MAP increases with age and the development of hypertension. This tends to mask the loss of sympathetic mediated pressor tone after ganglion blockade. By preventing this compensation we have shown that the sympathetically mediated component of blood pressure is elevated in SHRSP with established hypertension.
AGEING AND BLOOD PRESSURE REGULATION: DOSE‐RESPONSE RELATIONSHIPS FOR ANGIOTENSIN, BLOOD PRESSURE, ATRIAL NATRIURETIC PEPTIDE AND ALDOSTERONE IN NORMAL SUBJECTS OF VARYING AGES
Authors: Finn Wendy L. , Tunny Terry J. , Klemm Shelley A. , Ryan Susan J. , Gordon Richard D.
Published: June 2007

1. Infusion of increasing doses of angiotensin II (AII) in normal subjects sequentially increased blood pressure, aldosterone and atrial natriuretic peptide (ANP) levels.

2. The slope of ANP response to AII was positively correlated with basal ANP and with the slope of blood pressure response to AII (pressor slope) but not with age.

3. This is consistent with the response of ANP to AII being mediated partly by the rise in blood pressure, independent of ageing.

4. As expected in a selected normotensive population, there was no correlation between basal blood pressure and age, but pressor slope was positively correlated with age.

5. Thus, dose‐response relationships may be an index of age‐induced alterations in pressure regulatory mechanisms.
EFFECTS OF DIABETES ON DISPOSITION AND HEPATIC HANDLING OF CEFMETAZOLE IN RATS
Authors: Barrientos C. , González P. , Tuñón M. J. , Culebras J. M. , González‐Gallego J.
Published: June 2007

1. The effects of streptozotocin‐induced diabetes on disposition and hepatic handling of cefmetazole, a broad‐spectrum cephalosporin, were investigated in rats.

2. Male Wistar rats were pretreated with streptozotocin (60 mg/kg, i.p.) to induce uncontrolled diabetes. Fourteen days later bile flow was significantly reduced (12%) and bile acid secretion was significantly enhanced (87%) when compared with control animals.

3. Following intravenous injection of cefmetazole at a dose of 200 μmol/kg, maximal and cumulative biliary excretion of the antibiotic were significantly impaired in streptozotocin‐treated animals (27 and 22%, respectively).

4. Cefmetazole excretion into bile was accompanied by marked choleresis. The magnitude of bile flow increase was larger in control animals.

5. Total systemic clearance of the antibiotic was reduced (36%) and mean half‐life for the fast and slow phases of disposition increased (136 and 48%, respectively) in diabetic rats.

6. These changes were probably due to the diabetic condition of the animals because insulin treatment resulted in almost complete cofrection.
DIFFERENT RESPONSES TO ACETYLCHOLINE IN THE PRESENCE OF NITRIC OXIDE INHIBITOR IN RAT AORTAE AND MESENTERIC ARTERIES
Authors: Wu Chin‐Chen , Chen Shiu‐Jen , Yen Mao‐Hsiung
Published: June 2007

1. This study compared the relaxation induced by acetylcholine (ACh) in aortic and mesenteric arterial rings from Sprague‐Dawley (SD) rats in the presence and absence of inhibitors of the known endothelium‐derived relaxing factors.

2. ACh‐induced relaxations were completely blocked by methylene blue and N”‐nitro‐L‐arginine (LNNA) in aortae, whereas these were only partially attenuated by methylene blue and LNNA in mesenteric arteries.

3. This methylene blue‐resistant relaxation of ACh was partly attenuated by potassium channel blockers (tetraethylammonium and barium) but not affected by LNNA, indomethacin and calcium‐free solution.

4. These results suggest that there may be another endothelial relaxing factor which is not nitric oxide (NO), prostanoids or endothelium‐derived hyperpolarizing factor (EDHF) in mesenteric arteries but not in aortae. This unknown factor seems to be extracellular calcium ([Ca2+]o)‐independent.
DO ANGIOTENSIN CONVERTING ENZYME INHIBITORS LIMIT MYOCARDIAL INFARCT SIZE?
Authors: Miki Takayuki , Miura Tetsuji , Shimamoto Kazuaki , Urabe Kazuyuki , Sakamoto Jun , Iimura Osamu
Published: June 2007

1. Effects of captopril, ramiprilat and Hoe 140, a specific bradykinin receptor antagonist, on infarct size were assessed in a rabbit model of myocardial infarction.

2. Rabbits were untreated or pretreated with 0.5 mg/kg of captopril, 0.05 mg/kg of ramiprilat or 20 nmol/kg of Hoe 140 before 30 min coronary artery occlusion and 72 h reperfusion.

3. Captopril and ramiprilat treatment reduced systemic blood pressure by about 10 mmHg without alteration of heart rate, and the dose of Hoe 140 almost completely blocked hypotensive response to intravenous injection of bradykinin (100 ng/kg).

4. Infarct size expressed as percentage of area at risk was 44.5 ± 3.3% in the control group, 41.9 ± 1.6% in the captopril group, 51.8 ± 2.7% in the ramiprilat group and 46.7 ± 2.2% in the Hoe 140 group. All percentages were not significantly different.

5. These data suggest that angiotensin converting enzymes (ACE), with or without sulfhydryl groups do not limit myocardial infarct size and that endogenous bradykinin in ischaemic myocardium does not play a major protective role against ischaemic myocardial necrosis.
PLASMA FROM NORMAL PREGNANT WOMEN ALTERS THE REACTIVITY OF RABBIT AORTIC SMOOTH MUSCLE WITH FUNCTIONAL ENDOTHELIUM
Authors: Ezimokhai M. , Aloamaka C. P. , Cherian T. , Agarwal M. , Morrison J.
Published: June 2007

1. The effects of normal human pregnant plasma on the reactivity of rabbit aortic rings with documented endothelium have been studied. The rings were incubated in plasma from either normal pregnant or non‐pregnant women and the effects of incubation on their responses to noradrenaline (NA), calcium chloride stimulation and potassium chloride‐induced relaxation were examined.

2. There was no significant difference in the responses to NA in rings incubated in plasma from either pregnant or non‐pregnant women.

3. The responses of the rings, incubated in both types of plasma, to calcium chloride stimulation through receptor‐operated channels were similar, but rings incubated in plasma from pregnant women demonstrated decreased sensitivity and contractility to calcium chloride stimulation through voltage operated channels.

4. Potassium chloride‐induced relaxation was significantly enhanced in rings incubated in plasma from normal pregnant women. The pattern of the responses was unaltered by either de‐endothelialization or pretreatment of the rings with indomethacin.

5. The effects of plasma from pregnant women are similar to what has been reported as characteristic of vascular smooth muscle in normal pregnancy.
EFFECTS OF PEPTIDE HISTIDINE ISOLEUCINE ON PANCREATIC EXOCRINE SECRETION IN ANAESTHETIZED DOGS
Authors: Iwatsuki K. , Ren L.‐M. , Chiba S.
Published: June 2007

1. The effects of peptide histidine isoleucine (PHI) on pancreatic exocrine secretion were investigated in preparations of the isolated and blood‐perfused dog pancreas as compared with those of vasoactive intestinal peptide (VIP), secretin and glucagon.

2. Each peptide tested was injected intra‐arterially (i.a.) as a single bolus. Graded doses of PHI (3–300 nmol/kg), VIP (1–100 nmol/kg) and secretin (0.01–0.3 nmol/kg) caused dose‐dependent increases in the secretion of pancreatic juice and bicarbonate outputs, but had little effect on the protein outputs. Glucagon (0.1–10 μmol/kg) produced a bell‐shaped dose—response curve for the secretory rate, bicarbonate and protein outputs.

3. The secretory activity of 30 nmol/ kg of PHI corresponded roughly to that of 80 pmol/ kg of secretin, 9 nmol/kg of VIP and 0.6 μmol/kg of glucagon, respectively. Thus, based on administered dose, PHI was about 375 × less potent than secretin, 3 × less potent than VIP and 20 × more potent than glucagon.

4. The PHI‐ and VIP‐stimulated secretions were inhibited by a VIP antagonist, but not by a glucagon antagonist, SCH23390 (a dopamine D‐1 antagonist), L‐364718 (a cholecystokinin antagonist) or atropine.

5. Each peptide increased cyclic AMP concentration, but not cyclic GMP concentration, concomitant with the increase in pancreatic secretion.

6. From these results, it is concluded that PHI produces an increase in pancreatic secretion by acting on VIP‐preferring receptors on the exocrine pancreatic gland of the dogs. This may be mediated at least in part through the increase of intracellular cyclic AMP concentrations.
ANALYSIS OF SECRETION AND EXPRESSION OF PLATELET‐DERIVED GROWTH FACTOR IN CULTURED ENDOTHELIAL CELLS FROM STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Iihara Koji , Sasahara Masakiyo , Saeki Yukikazu , Hashimoto Nobuo , Kikuchi Haruhiko , Hazama Fumitada
Published: June 2007

1. We characterized the endothelial cell‐derived growth factors of SHRSP and Wistar Kyoto rats (WKY), respectively and found that platelet‐derived growth factor (PDGF)‐B chain related growth factor constituted a major portion of the mitogenic activity of the conditioned media of endothelial cells from both animals. There were no remarkable qualitative differences between the endothelial cell‐derived growth factors of SHRSP and WKY.

2. Northern analysis revealed that the expression of PDGF‐B chain was 2–4‐fold enhanced in cultured aortic endothelial cells of SHRSP. This enhanced expression of PDGF‐B chain, which may be induced under chronic hypertensive conditions, is suggested to contribute to the increase in endothelial cell‐derived growth factors reported in this animal.
EFFECT OF ARGININE VASOPRESSIN AND PARATHYROID HORMONE‐RELATED PROTEIN ON RENAL FUNCTION IN THE OVINE FOETUS
Authors: Horne Rosemary S. C. , MacIsaac Richard J. , Moritz Karen M. , Tangalakis Kathy , Wintour E. Marelyn
Published: June 2007

1. The effects of intravenous infusions of arginine vasopressin (AVP), parathyroid hormone‐related protein (PTHrP) and AVP + PTHrP on renal function in intact ovine foetuses at 100–125 days of gestation were examined.

2. A low dose of AVP (5.5 ± 0.9 pmol/h) increased plasma AVP concentrations from 0.6 pmol/L to 2.1 ± 0.4 pmol/L (mean ± s.e.m; n= 8). This dose caused a significant reduction in free water clearance (CH2O; P<0.001), without any significant change in fetal arterial blood pressure, glomerular filtration rate (GFR), or the urinary excretion rates of sodium, calcium or 3', 5'‐cyclic adenosine monophosphate (CAMP).

3. Infusions of PTHrP (1 nmol/h), with or without 1 nmol bolus dose, significantly increased (P<0.05) urine osmolality (Uosm), but did not synergize with AVP in reducing CH2O.

4. It is concluded that AVP and PTHrP do not act synergistically on the kidney of the intact ovine foetus.
EFFECT OF XANTHINE DERIVATIVES ON CHEMOTACTIC POLYPEPTIDE‐INDUCED SUPEROXIDE AND ENZYME RELEASE FROM HUMAN POLYMORPHONUCLEAR LEUCOCYTES
Authors: Hirano Tsunekazu , Ando Morihide , Suzuki Kenji , Furui Hidehiko , Miyamoto Kenichi , Takagi Kenzo
Published: June 2007

1. We investigated the effects of new xanthine derivatives, 1‐methyl‐3‐propyl xanthine (MPX) and 1,3‐dipropyl xanthine (DPX), and several other xanthine derivatives on N‐formyl‐methionyl‐leucyl‐phenylalanine‐induced superoxide and lysozyme release from human polymorphonuclear leucocytes (PMN).

2. MPX and DPX at low concentrations (10−8‐10−9 mol/L) inhibited superoxide release from PMN by a maximum of 31.2 ± 10.6% and 49.8 ± 10.4% (mean ± s.d.), respectively, and 10−3 mol/L concentrations completely inhibited the release reactions (4.8 ± 1.2 and 7.6 ± 2.5% of control level). At 10−5 mol/ L, however, the inhibition did not occur (99.9 ± 7.3 and 110.2 ± 15.8% of control level). When PMN was pre‐incubated with adenosine deaminase (ADA, 0.1 U/mL), superoxide release from PMN was inhibited in a dose‐dependent manner by MPX and DPX and the interruption of the inhibition at 10−5 mol/L was not observed.

3. Lysozyme release from PMN was inhibited by MPX at low concentrations (10−7‐10−6 mol/L) and high concentrations (10−3 mol/L). However 10−4 mol/L of MPX facilitated the release (23.7 ± 27.0%). When pretreated with ADA (0.1 U/mL), MPX suppressed lysozyme release in a dose‐dependent manner and the facilitation of the release at 10−4 mol/L was not observed.

4. When comparing effects of some other xanthine derivatives on superoxide release, the interruption of the inhibition of superoxide release at 10−5 mol/L was commonly observed among xanthine derivatives with adenosine A2 antagonism.

5. The results suggest that adenosine A2 antagonism of xanthine derivatives may interfere with their anti‐inflammatory effects at therapeutic concentrations (10−5‐10−4 mol/L).
EFFECT OF NICORANDIL ON POST‐ISCHAEMIC CONTRACTILE DYSFUNCTION IN THE HEART: ROLES OF ITS ATP‐SENSITIVE K’ CHANNEL OPENING PROPERTY AND NITRATE PROPERTY
Authors: Iwamoto Toshihiro , Miura Tetsuji , Urabe Kazuyuki , Itoya Masao , Shimamoto Kazuaki , Iimura Osamu
Published: June 2007

1. This study aimed to characterize the effect of nicorandil (NC) on myocardial stunning and the role of ATP‐sensitive K+ (Katp) channel opening property in its cardioprotective action.

2. In open‐chest anaesthetized rabbits, myocardial stunning was induced by 10 min of coronary occlusion followed by 30 min of reperfusion. As an index of regional contractile function, systolic thickening fraction (TF) was measured by an epicardial Doppler sensor. The doses of NC (10 μg/kg per min) and nitroglycerin (TNG) (1 μg/kg per min) were selected not to lower the systemic blood pressure significantly.

3. In the untreated controls, TF at 30 min after reperfusion was 46.4 ± 2.9% of the baseline value, indicating myocardial stunning. Both NC and TNG significantly improved post‐ischaemic recovery of TF when administered during the pre‐ischaemic and post‐ischaemic periods (TF = 68.2 ± 6.4%, 64.7 ± 2.3%, respectively). However, when their infusion was restricted to a pre‐ischaemic 10 min period, TF recovery was improved by NC, but not by TNG (63.4 ± 7.9%, 40.9 ± 6.2%, respectively).

4. Pretreatment with glibenclamide (GL; 0.3 mg/kg) did not influence the recovery of TF after the 10 rnin ischaemia (TF = 52.4 ± 3.9% at 30 min after reperfusion). However, after the GL injection, a cardioprotective effect from nicorandil pretreatment was not detected (TF = 51.3 ± 1.7%).

5. These results suggest that nicorandil protects the myocardium against stunning by opening the Katp channel when it is given before ischaemia, and that the nitrate property of nicorandil may also play a role during the reperfusion period in attenuation of post‐ischaemic contractile dysfunction.
PLASMA RENIN ACTIVITY DURING HYPOTENSIVE RESPONSES TO ELECTRICAL STIMULATION OF CAROTID SINUS NERVES IN CONSCIOUS DOGS
Authors: Peters Tim K. , Kaczmarczyk Gabriele
Published: June 2007

1. The interaction of electrical stimulation of the carotid sinus nerves (carotid sinus nerve stimulation, CSNS) with mechanisms of renin release was studied in conscious and unrestrained resting beagle dogs receiving a standardized diet (sodium intake, 4.5 mmol/kg bodyweight (bw); water intake, 91 mL/kg bw).

2. By CSNS, mean arterial blood pressure (MAP) was lowered for periods of 20 min to levels between 101 ± 4 and 56 ± 5 mmHg.

3. In another group of conscious dogs, renal perfusion pressure (RPP) was lowered to 95 ± 4 mmHg for periods of 20 min by partial suprarenal aortic occlusion in order to assess the influence of a reduced RPP on plasma renin activity (PRA) without concomitant CSNS.

4. During CSNS, PRA increased markedly (> 100%) only when MAP was reduced below 75 mmHg.

5. With aortic constriction and an RPP of 95 mmHg, the increase in PRA was 955%, which is more than three‐fold higher than the increase in PRA during CSNS at MAP levels <65 mmHg (314%).

6. The observed responses indirectly support the hypothesis that basal activity in efferent renal nerve discharge is present even at rest and can be inhibited by CSNS, and furthermore suggests that CSNS attenuated the pressure‐dependent renin release.
RENAL DENERVATION POTENTIATES THE NATRIURETIC AND DIURETIC EFFECTS OF ATRIAL NATRIURETIC PEPTIDE IN ANAESTHETIZED RABBITS
Authors: Christy I. J. , Denton K. M. , Anderson W. P.
Published: June 2007

1. The role of the renal nerves in modulating the action of atrial natriuretic peptide (ANP) in the kidney was studied by comparing the responses to ANP in innervated and surgically denervated kidneys in anaesthetized rabbits.

2. A low dose of ANP (0.05 μg/kg per min, i.v.) was used to minimize the confounding effects of systemic hypotension.

3. The natriuretic and diuretic responses to ANP were significantly greater in denervated kidneys than in kidneys with intact innervation. Sodium excretion from denervated kidneys rose by 7.49 ± 3.11 μmol/min in response to ANP (‐55%, P<0.05) compared to 0.84 ± 0.59 μmol/min (‐28%, NS) in innervated kidneys. Urine flow increased markedly in denervated kidneys by 73.2 ± 29.9 μmol/min (‐60%, P<0.05) but not in innervated kidneys.

4. Fractional sodium excretion increased significantly in denervated kidneys in response to ANP (median 2.3% to median 3.0%, P<0.05).

5. Renal blood flow, glomerular filtration rate (GFR) and glomerular capillary pressure were unchanged in response to ANP in either denervated or innervated kidneys. Pre‐glomerular vascular resistance fell in denervated kidneys during ANP infusion.

6. The natriuresis and diuresis observed in the denervated kidneys, due to an increased fractional excretion of sodium without increases in GFR or glomerular capillary pressure, is consistent with effects of ANP on tubular reabsorption of sodium.

7. Thus, ANP produced a natriuresis and diuresis at a low dose in denervated but not in innervated kidneys. This indicates that reflex activation of renal nerves may antagonize the renal effects of ANP.
EFFECTS OF CALCIUM‐ AND ETa‐RECEPTOR ANTAGONISTS ON ENDOTHELIN‐INDUCED VASOCONSTRICTION AND LEVELS OF ENDOTHELIN IN THE HUMAN INTERNAL MAMMARY ARTERY
Authors: Liu James J. , Casley David , Wojta Johann , Gallicchio Marisa , Dauer Ray , Johnston Colin I. , Buxton Brian F.
Published: June 2007

1. The effects of the ETA receptor antagonist BQ123 and dihydropyridine calcium antagonists on the vasoconstrictor effect of endothlin‐1 (ET‐1) were studied in human isolated internal mammary artery (IMA). The effect of the calcium antagonist, nisoldipine, on ET‐1 levels has also been examined in cultured IMA endothelial cells (IMAEC).

2. The results showed that BQ123 and the calcium antagonists nisoldipine, isradipine, nitrendipine and nifedipine fully relaxed IMA precontracted with 3 nmol/L ET‐1 with the EC50 values of 7.18 ± 0.09 (‐log mol/L) for BQ123, and 7.68 ± 0.07, 7.02 ± 0.12, 6.96 ± 0.08 and 6.89 ± 0.09 for the calcium antagonists, respectively.

3. Pretreatment of IMA with 10, 30, 100 and 300 nmol/L nisoldipine significantly depressed the maximal response (Max; 88.3 ± 5.1, 75.2 ± 4.9, 59.3 ± 5.6 and 56.2 ± 4.8% of maximal noradrenaline response versus 99.1 ± 13.2% in control, P<0.01) of IMA to ET‐1 without a significant change in the EC50 values.

4. Pretreatment of IMA with 300 nmol/L BQ123 significantly increased both the EC50 (7.97 ± 0.09 vs 8.36 ± 0.08 in the control, P<0.05) and the Max (138.1 ± 10.2%vs the control, P< 0.01) of IMA to ET‐1.

5. Incubation of IMAEC with nisoldipine for 7h resulted in a dose‐dependent (10−8–10−5 mol/L) reduction up to 93.1% in ET levels in the conditioned media.

6. ET levels in the cell lysates were not detectable either in the absence or in the presence of nisoldipine, suggesting the reduction of ET levels in the media could be due to inhibition of ET synthesis.

7. In conclusion, these studies demonstrate that: (i) both BQ123 and the calcium antagonists are potent relaxant agents of human IMA precontracted with ET‐1; (ii) BQ123 also increases the Max of IMA to ET‐1 and the mechanism is unknown; (iii) the calcium antagonist nisoldipine reduces ET levels in the cultured human IMAEC.
EFFECTS OF ANTI‐EMETICS ON WATER EXCRETION IN HUMANS
Authors: Phillips P. A. , Burrell L. M. , Risvanis J. , Stephenson J. , Johnston C. I. , Hutchins A‐M.
Published: June 2007

1. The anti‐emetic drug metoclopramide has been shown to stimulate secretion of the antidiuretic hormone arginine vasopressin. Since metoclopramide is used to treat nausea, which is another potent stimulus to vasopressin secretion, the aim of this study was to determine whether metoclopramide might limit free water excretion and so cause hyponatraemia.

2. Metoclopramide 20 mg (0.2–0.3 mg/kg), prochlorperazine 12.5 mg (0.1–0.2 mg/kg) and placebo were administered intravenously in a double blind randomized crossover way at 2 week intervals and the effects on urine flow rate, plasma osmolality, thirst ratings and plasma sodium and atrial natriuretic peptide concentrations determined in water‐loaded (10 mL/kg) healthy young men.

3. There were no differential effects on any variable of either drug versus placebo.

4. These results indicate that metoclopramide is unlikely to cause any significant water retention in a clinical setting or precipitate hyponatraemia.
DOES PHOSPHORYLATION AFFECT TRANSPORT OF INORGANIC PHOSPHATE?
Authors: Mary P. L. , Rao J. Prakasa
Published: June 2007

1. This study investigated the effects of fructose and 2‐deoxyglucose on the uptake and release of phosphate from everted intestinal sacs of mice.

2. Both the sugars significantly decreased the release of phosphate without affecting the uptake.

3. Succinate and fumarate were able to partially reverse the inhibition of phosphate release exerted by fructose but not that exerted by 2‐deoxyglucose.

4. Pre‐loading with mannoheptulose, a known inhibitor of hexokinase, improved the release of phosphate in the presence of either of these sugars.

5. Adrenaline, known to inhibit phosphorylation of 2‐deoxyglucose, reduced the inhibition exerted by this sugar on phosphate release.

6. These results indicate that the inhibition of phosphate release caused by these sugars may be due to the trapping of free phosphate during their metabolism in the gut wall.
AUTACOIDS AND CONTROL OF HUMAN PLACENTAL BLOOD FLOW
Authors: Boura A. L. A. , Walters W. A. W. , Read M. A. , Leitch I. M.
Published: June 2007

1. Humans have a haemochorial, villous placenta. Uterine blood passes through maternal sinuses, bathing placental villi through which fetal blood circulates. Blood flow through each circulation is high and vascular resistance low. This haemodynamic situation is essential for efficient placental function.

2. The low placental vascular resistance is due to a lack of nervous influences together with pregnancy‐induced changes promoting vasodilatation. Increases occur in output of the vasodilators prostacyclin and nitric oxide and also in membrane sodium pump activity.

3. Many autacoids are present in umbilical blood. Fetal vessels of the placenta develop intense vasoconstriction in the presence of some autacoids, such as thromboxane A2 and prostaglandins F2α and E2, and respond weakly to others, such as angiotensin II and 5‐hydroxytryptamine. Nevertheless, vasodilator influences predominate.

4. The diseases of pre‐eclampsia and fetal growth retardation are associated with reduced output of nitric oxide and prostacyclin and with increased production of thromboxane A2 and endothelin‐1. These changes promote vasoconstriction, increased vascular sensitivity to vasoconstrictor stimuli, platelet aggregation and intravascular coagulation, retarding blood flow and feto‐placental growth.

5. Aspirin and glyceryl trinitrate have been investigated for possible therapeutic use in pre‐eclampsia and fetal growth retardation. Improved drug therapy is likely as knowledge increases of the importance of autacoids in normal placental function and in the changes that occur during disease.
THERAPEUTIC RESTORATION OF ENDOTHELIAL FUNCTION IN HYPERCHOLESTEROLAEMIC SUBJECTS: EFFECT OF FISH OILS
Authors: Chin Jaye P. F. , Dart Anthony M.
Published: June 2007

1. Endothelial dysfunction, evidenced as an impaired response to acetylcholine, is well documented in hypercholesterolaemic subjects. We examined the ability of dietary supplementation with fish oils to restore endothelial function in forearm resistance vessels in these patients and compared this with restoration by lipid‐lowering therapy.

2. Responses of forearm blood flow to acetylcholine (4.6, 9.25, 18.5 and 37 μg/min) and sodium nitroprusside (200, 400, 800 and 1600 ng/min) were obtained using forearm venous occlusion plethysmography in nine hypercholesterolaemic and seven age‐matched control subjects. The dose—response curve to acetylcholine was significantly blunted in hypercholesterolaemic subjects when compared with controls (P<0.001). Responses to sodium nitroprusside were not different between the two groups (P= 0.37).

3. Lipid‐lowering therapy decreased total plasma cholesterol levels by 33% and significantly augmented the responses to acetylcholine (P = 0.001) but not to sodium nitroprusside in the hypercholesterolaemic subjects.

4. Dietary supplementation with fish oils had no effect on either total or low density lipoprotein‐cholesterol but significantly augmented the responses to acetylcholine (P= 0.011) in hypercholesterolaemic subjects. Responses to sodium nitroprusside were not altered (P= 0.94).

5. This study shows that endothelium‐dependent relaxation is impaired in subjects with high cholesterol levels and that this impairment can be reversed by lowering low density lipoproteins (LDL) cholesterol levels. In addition, we demonstrate that restoration of endothelial function can occur without changes in LDL levels, by dietary supplementation with fish oils.
LONG‐TERM CLENBUTEROL ADMINISTRATION ALTERS THE ISOMETRIC CONTRACTILE PROPERTIES OF SKELETAL MUSCLE FROM NORMAL AND DYSTROPHIN‐DEFICIENT MDX MICE
Authors: Hayes Alan , Williams David A.
Published: June 2007

1. This study was designed to establish whether long‐term treatment with the powerful anabolic agent clenbuterol has beneficial effects on dystrophin‐deficient skeletal muscle function.

2. Normal (C57BL/10) and dystrophic (mdx) mice were administered clenbuterol (2 mg/kg per day) for 15 weeks. At 20 weeks of age, the extensor digitorum longus (EDL) and soleus muscles were removed, and their contractile and histochemical properties analysed.

3. Absolute and relative muscle masses were larger (P<0.001) in mdx compared to C57BL/10 mice. These larger muscles produced larger absolute forces (P<0.01) in the soleus of mdx mice compared to normal mice. Relative tetanic force was also larger (P<0.05) in the soleus of mdx mice. In contrast, the absolute tetanic tension of the EDL was reduced (P<0.01) in mdx mice compared to C57BL/10 mice, and both relative twitch and tetanic tensions were also lower (P<0.001) in mdx mice.

4. Clenbuterol increased the lean muscle mass in both normal (10%, P<0.05 and 20%, P<0.01 for the EDL and soleus, respectively) and dystrophic (7%, P<0.05 and 11%, P<0.01) groups. Twitch contraction times were significantly faster in both the EDL (P<0.001) and soleus (P<0.01) muscles following clenbuterol administration, supported by fibre‐type transitions towards fast‐twitch fibres. Relative force levels of the soleus muscle of both C57BL/10 (40%, P<0.01) and rndx (20%, P<0.01) mice were increased significantly following clenbuterol treatment. No changes in the absolute or relative forces of the EDL muscles were observed in response to clenbuterol administration.

5. Clenbuterol was thus able to increase the force output of a slow‐twitch, mixed (hence humanlike) muscle but not fast‐twitch muscle from mdx mice. The results lend tentative support to the potential role of clenbuterol as an anabolic agent in the treatment of muscle wasting diseases.
ANGIOTENSIN RECEPTORS IN CARDIOVASCULAR DISEASES
Authors: Brown Lindsay , Sernia Conrad
Published: June 2007

1. Angiotensin II (AII) plays a major role in cardiovascular function via direct actions on the vasculature, kidney, adrenal, heart, brain and sympathetic nerves. The cellular effects of AII are extensive and encompass hypertrophy, hyperplasia and the deposition of extracellular matrix.

2. The actions of AII are mediated by the AT1 and AT2 membrane receptor subtypes, and additional forms of each subtype. Evidence is emerging that selective changes in AII receptor subtypes occur in cardiovascular diseases.

3. Thyroid dysfunction increased cardiac, liver and kidney AII receptor density but decreased adrenal gland receptor density. In the heart, there was a selective increase in AT2 receptor density.

4. Diabetes increased cardiac, liver and adrenal gland AII receptor densities but decreased kidney receptor density.

5. Hypertension increased AII receptor density in the heart and kidney. A corresponding increase in receptor mRNA was prevented by selective AT1 receptor antagonists.

6. The human heart contained AII receptors in all chambers; right atrial receptor density was increased in coronary artery bypass graft patients.

7. The presence of AII receptor changes in these models of cardiac hypertrophy and hypertension raises the possibility of using orally active, subtype‐selective agonists and antagonists to treat particular forms of cardiovascular diseases.
KYNURENIC ACID, AN ENDOGENOUS GLUTAMATE ANTAGONIST, IN SHR AND WKY RATS: POSSIBLE ROLE IN CENTRAL BLOOD PRESSURE REGULATION
Authors: Kapoor Vimal , Kapoor Ranjna , Chalmers John
Published: June 2007

1. Kynurenine aminotransferase catalyzes the conversion of kynurenine to kynurenic acid, an endogenous antagonist of excitatory amino acid receptors. The kynurenic acid content and kynurenine aminotransferase activity was measured in micro‐dissected regions of spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar‐Kyoto rats: WKY).

2. Of the brain regions examined the highest kynurenine aminotransferase activity was found in the medulla followed by the olfactory bulb and the cerebellum, with the spinal cord showing the lowest activity.

3. All samples from SHR showed greatly reduced kynurenine aminotransferase activity compared to WKY. These reductions were most pronounced in the medulla and spinal cord, approximately 45–55%, and lowest in the cerebellum and olfactory bulbs, approximately 25–30%.

4. The kynurenic acid content of the rostral and caudal medulla as well as the spinal cord was also significantly lower in SHR.

5. These results suggest that there may be a deficiency in the kynurenic acid content and kynurenine aminotransferase activity in the SHR.

6. Given the accumulating evidence of the importance of medullary glutamatergic pathways in the control of blood pressure, as well as the higher sensitivity of cardiovascular neurons of SHR to applied glutamate, it seems possible that endogenous kynurenic acid in the brain may play a role in the control of blood pressure and the pathogenesis of experimental hypertension in the SHR.
FOREWORD
Authors: DSc Brian J. Morris
Published: June 2007

GENES & GENETICS SATELLITE SYMPOSIUM
COMPARISON OF SALT SENSITIVITY OF MALE AND FEMALE F2 PROGENY FROM CROSSES BETWEEN WHY AND SHRSP RATS
Authors: Nara Yasuo , Ikeda Katsumi , Nabika Toru , Sawamura Makoto , Mano Masayuki , Endo Jiro , Yamori Yukio
Published: June 2007

1. The present study compared the salt sensitivity of male and female F2 progeny obtained from crosses between Wistar‐Kyoto/Izumo rats and stroke‐prone spontaneously hypertensive rats (SHRSP A3b/ Izm) after salt loading for 7 months.

2. Average systolic blood pressure in male F2 progeny was 10 mmHg higher than that of female F2 progeny at 5 months without salt loading.

3. The blood pressure in male F2 progeny was raised significantly 2 months after salt loading, but there was no further significant change in blood pressure even though salt loading was continued for 5 months.

4. In female F2 progeny, however, a significant change in systolic blood pressure was observed 1 month after salt loading and there was a further significant rise in blood pressure over 6 months.

5. Angiotensin I‐converting enzyme and RR 1023 loci were strongly linked to systolic and diastolic blood pressures in the male but not the female F2 progeny after salt loading for 7 months.

6. We therefore speculate that the hormonal difference between sexes might influence salt sensitivity in the SHRSP.
GENES OF STRESS IN EXPERIMENTAL HYPERTENSION
Authors: Hamet P. , Sun Y. L. , Malo D. , Kong D. , Křen V. , Pravenec M. , Kuneš J. , Dumas P. , Richard L. , Gagnon F. , Tremblay J.
Published: June 2007

1. A significant portion of blood pressure variance is modified by the environment.

2. The present report summarizes evidence that: (i) the environmental response is genetically determined; (ii) various stressors can evoke a differential response in hypertensive animals and constitute its intermediate phenotypes; (iii) the response to heat stress can be assigned to a single ‘thermosensitivity’ locus; (iv) candidate genes of susceptibility to environmental stresses are member(s) of the heat stress gene (HSP) gene families; (v) a restriction fragment length polymorphism ofhsp70 and a single base mutation in the 3′‐untranslated region of hsp27 are associated with hypertension in recombinant inbred strains.

3. In conclusion, HSP gene variants may be causative in susceptibility to hypertension.
MOLECULAR GENETICS OF THE SA GENE
Authors: Iwai Naoharu , Inagami Tadashi , Kinoshita Masahiko
Published: June 2007

1. We have recently identified a candidate gene for rat genetic hypertension, termed Sa, by identifying an mRN A species that shows markedly higher expression in the kidneys of spontaneously hypertensive rats (SHR) than in those of Wistar‐Kyoto rats (WKY).

2. Subsequent genetic co‐segregation analyses by ourselves and others indicated that the Sa gene locus did indeed influence blood pressure. Moreover, in a preliminary association study, we found an association of a polymorphism of the human Sa gene with essential hypertension.

3. Further studies to identify functions of the Sa gene products are required before reaching a definite conclusion.
FREQUENCIES OF VARIANTS OF CANDIDATE GENES IN DIFFERENT AGE GROUPS OF HYPERTENSIVES
Authors: Zee Robert Y. L. , Bennett Craig L. , Schrader Andrew P. , Morris Brian J.
Published: June 2007

1. In severe, familial hypertension, we have reported that the proportion of patients homozygous for the deletion allele of an insertion/deletion polymorphism of the angiotensin I‐converting enzyme gene is markedly decreased in older age groups, suggesting that this genotype is associated with increased risk of premature death. The aim of the present study was to examine the relationship with age, of variants of other genes that encode proteins having an influence on the cardiovascular system.

2. Genotypes of 13 different variants at 12 relevant genetic loci were determined by either Southern blotting, followed by hybridization probing, or polymerase chain reaction techniques, as appropriate, using genomic DNA extracted from blood leukocytes. Genotype numbers were then assigned to the age categories of < 50, 50–59 and ≥60 years.

3. Polymorphisms at the atrial natriuretic factor, antithrombin III, renin, angiotensinogen, neuropeptide‐Y Y1 receptor, insulin, α2‐adrenoceptor, β1‐adrenoceptor, growth hormone, low density lipoprotein receptor, insulin receptor and renal kallikrein gene loci were found to display similar allele frequencies in each age group of hypertensives, as well as in normotensive controls.

4. In conclusion, we were unable to detect any difference with age for a range of variants of genes whose products have cardiovascular significance, suggesting that, like most polymorphisms, they carry no selective survival advantage or disadvantage in the hypertensive and normotensive population groups studied.
LYSOSOMAL IRON ACCUMULATION AND TUBULAR DAMAGE IN RAT PUROMYCIN NEPHROSIS AND AGEING
Authors: Harris David C. H. , Tay Ching , Nankivell Brian J.
Published: June 2007

1. Energy dispersive X‐ray spectrometry was used to examine the relationship between proteinuria and increased urinary iron excretion, and structural and functional damage in puromycin nephrosis.

2. After 11–12 days rats treated with puromycin (10 mg/100g, i.v.i.) had greater proteinuria (211.6 ± 35.7 mg/day, mean ± s.e.m.) and urinary iron excretion (15.4 ± 2.2 μg/day) than salinetreated controls (14.5 ± 1.4 mg/day and 1.1 ± 0.2 μg/day, respectively, both P<0.001).

3. On day 13, mean lysosomal iron concentration of proximal tubular cells (306.6 ± 64.5 vs 11.9 ± 8.6 mg%, P<0.001), and proximal tubular cell damage assessed semi‐quantitively (1.17 ± 0.10 vs 0.62 ± 0.10, P<0.001) were higher and creatinine clearance (0.15 ± 0.01 vs 0.29 ± 0.02 mL/min perg kidney weight, P<0.001) lower than in control rats.

4. At days 35, 60 and 360 there were no differences in any of the measured parameters between rats treated with puromycin or saline, and in both groups proteinuria, tissue damage and lysosomal iron concentration increased with time.

5. Lysosomal iron accumulation was the only independent predictor of both functional and structural damage.

6. In conclusion, the apparent association between proteinuria and tubulo‐interstitial damage in puromycin nephrosis, and with ageing, is best explained by factors associated with accumulation of iron within lysosomes of proximal tubule cells.
TRANSPLANTATION STUDIES OF THE ROLE OF THE KIDNEY IN LONG‐TERM BLOOD PRESSURE REDUCTION FOLLOWING BRIEF ACE INHIBITOR TREATMENT IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Harrap Stephen B. , Wang Bao‐Zhong , MacLellan Donald G.
Published: June 2007

1. Brief treatment with angiotensin‐converting enzyme (ACE) inhibitors in young spontaneously hypertensive rats (SHR) causes a persistent reduction in blood pressure associated with a relatively selective reduction in renal vascular resistance.

2. To study the possible role of the kidney in this long‐term hypotensive effect, we transplanted kidneys from untreated SHR into SHR that had been treated with perindopril (3 mg/kg per day) between 6 and 10 weeks of age and also transplanted kidneys from perindopril‐pretreated SHR into untreated SHR. After transplantation, the remaining native kidney was removed so that only donor kidneys remained.

3. Untreated SHR that received kidneys from perindopril‐pretreated SHR showed an initial fall in blood pressure followed by a rapid increase in pressure, weight loss and early death.

4. The transplantation of kidneys from control SHR into perindopril‐pretreated SHR resulted in a rise in blood pressure that obviated the long‐term reduction seen normally in these animals.

5. Kidneys from perindopril‐pretreated SHR may be susceptible to the high blood pressure in untreated SHR.

6. The blood pressure increase in perindopril‐pretreated SHR that accompanies substitution of the native kidneys by kidneys from untreated SHR further supports the hypothesis that the kidney is responsible for the long‐term pressure effects following ACE inhibition in young SHR.
EFFECT OF TRANSFORMING GROWTH FACTOR‐β1 ON PLATELET‐DERIVED GROWTH FACTOR RECEPTOR BINDING AND GENE EXPRESSION IN VASCULAR SMOOTH MUSCLE CELLS FROM SHR AND WKY RATS
Authors: Agrotis Alex , Saltis John , Bobik Alex
Published: June 2007

1. This study examined the effects of transforming growth factor‐βl (TGF‐β1) on platelet‐derived growth factor‐BB (PDGF‐BB)‐stimulated DNA synthesis, [125I]‐PDGF‐BB receptor binding and PDGF‐β receptor mRNA expression in vascular smooth muscle cells (VSMC) isolated from Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).

2. TGF‐β1 inhibited by 40% DNA synthesis stimulated by PDGF‐BB in VSMC from WKY rats but potentiated by 20% growth factor‐stimulated DNA synthesis in VSMC from the SHR.

3. Since the difference in effect of TGF‐β1 could not be attributed to differential regulation of [125I]‐PDGF‐BB binding activity and PDGF‐β receptor mRNA expression, it is suggested that alterations in intracellular signalling pathways may account for the differential effects of TGF‐β1 on PDGF‐BB‐stimulated DNA synthesis in VSMC from SHR and WKY rats.
AUGMENTATION OF BARORECEPTOR REFLEX FUNCTION BY ORAL CALCIUM SUPPLEMENTATION IN ESSENTIAL HYPERTENSION
Authors: Dazai Yasunobu , Iwata Takeru , Hiwada Kunio
Published: June 2007

1. We studied the effect of oral calcium supplementation (1.0 g/day) for 1 week on baroreceptor reflex function and the lability of blood pressure in association with the changes in autonomic nervous activity in 14 hospitalized patients with mild to moderate essential hypertension (nine males and five females, mean age of 56 ± 11.2 (s.d.) years).

2. Baroreceptor reflex sensitivity (BRS) was determined by the change in R‐R intervals in response to the pressor response induced by phenylephrine injection. We measured coefficient of variation of R‐R interval (CVr‐r) and urinary excretion of catecholamines to evaluate the mechanism of change in BRS. We also used coefficient of variation of blood pressure (CVBP) and error of single cosinor analysis as parameters for lability of 24‐h blood pressure.

3. The means of 24‐h systolic and diastolic blood pressures showed no significant changes after calcium supplementation for 1 week. BRS and CVR‐R were significantly increased by calcium supplementation. Daily excretions of norepinephrine and epinephrine corrected by creatinine were unchanged. Both CVbp and error of 24‐h systolic blood pressure showed a significant decrease after calcium treatment.

4. These results indicate that oral calcium supplementation augments baroreceptor reflex function, in part through an enhancement of parasympathetic nervous activity, resulting in reduction of the lability of blood pressure in patients with mild to moderate essential hypertension.
INTERACTIONS BETWEEN 5‐HYDROXYTRYPTAMINE, NORADRENALINE AND THE THROMBOXANE‐A2 MIMETIC U44069 IN THE MARMOSET ISOLATED AORTA
Authors: Dyer S. M. , Bexis S. , Mano M. T. , de la Lande I. S. , Frewin D. B. , Head R. J.
Published: June 2007

1. The effects of 5‐hydroxytryptamine (5‐HT) in the absence and presence of noradrenaline (NA) or the thromboxane‐A2 mimetic, U44069, were investigated in ring preparations of marmoset aorta.

2. 5‐HT (0.001‐10 μmol/L) produced little or no contractile response in preparations at basal tone. When the tone was elevated to 50% of maximum with NA the predominant response to 5‐HT was relaxation. The 5‐HT2 receptor antagonist LY53857 (0.1 μmol/L) unmasked a contractile response to low concentrations of 5‐HT (0.01 ‐ 1.0 μmol/L) and reduced relaxation to high concentrations of 5‐HT (1.0‐10 μmol/L) in vessels precontracted with NA.

3. In U44069‐contracted vessels, 5‐HT was contractile in the range 0.01‐1 μmol/L and relaxant in concentrations of 6.0‐10.0 μmol/L. Ketanserin (1.0 μmol/L) had no effect on the contraction or relaxation to 5‐HT.

4. The relaxant response to 5‐HT was not significantly diminished in endothelium‐impaired arteries.

5. In conclusion, 5‐HT exerts complex inhibitory and excitatory actions on the marmoset aorta. The inhibitory actions are not endothelium‐dependent and the excitatory actions do not appear to involve the 5‐HT2 receptor.