bluuebunny/crossref_metadata_2025_split huggingface dataset:
CARDIAC HYPERTROPHY IN DIABETIC SPONTANEOUSLY HYPERTENSIVE RATS: ROLE OF ANGIOTENSIN II?
Authors: Black M Jane , Briscoe Todd , Bertram John F. , Jackson Bruce , Johnston Colin I. 
Published: June 2007

SUMMARY1. In the present study the role of angiotensin II (AngII) in the development of cardiac hypertrophy in diabetes combined with hypertension was investigated.2. Diabetes was induced in 8‐week‐old male spontaneously hypertensive rats (SHR) by intravenous injection of streptozo‐tocin (45 mg/kg body weight). Diabetic SHR were treated with the angiotensin‐converting enzyme (ACE) inhibitor ramipril at a dose of 0.4 mg/kg per day.3. Twelve weeks following the onset of diabetes, hearts were arrested in diastole and were perfusion‐fixed. The right ventricle and left ventricle plus septum were weighed and the volume of the ventricular walls was determined using the Cavalieri principle.4. Induction of diabetes in SHR led to a significant reduction in bodyweight compared with non‐diabetic control SHR and this was not affected by ramipril treatment The development of hypertension was not as great in diabetic SHR compared with controls, such that at 12 weeks following the onset of diabetes systolic blood pressures (SBP) averaged 191 ± 3 and 230 ± 4 mmHg in diabetic SHR and controls, respectively. Ramipril treatment significantly lowered SBP in diabetic SHR.5. The left ventricle plus septum volume:bodyweight ratio (LV vol:BW) was significantly higher in diabetic SHR compared with controls (3.83 ± 0.19 and 3.26 ± 0.16 mm3/g, respectively). Ramipril treatment did not affect growth of the left ventricle in diabetic SHR with the LV vol:BW ratio averaging 3.95 ± 0.14 mm3/g. Similar trends on growth were observed in the right ventricle.6. In conclusion, the development of cardiac hypertrophy in diabetic SHR appears to occur by mechanisms independent of AngII and the elevation of blood pressure.
STIMULATION OF THE GASTRIC SODIUM MONITOR REDUCES HEPATIC ANGIOTENSIN‐CONVERTING ENZYME ACTIVITY
Authors: Duggan KA , Ye VZC 
Published: June 2007

SUMMARY1. The natriuresis engendered by stimulation of the gastric sodium monitor is mediated in part by a decrease in the circulating concentration of angiotensin II (AngII). This decrease is due to a decrease in synthesis rather than to an increase in metabolism. We investigated the role of changes in plasma and hepatic angiotensin‐converting enzyme (ACE) activity in this decrease in AngII synthesis.2. Male Sprague‐Dawley rats were equilibrated on a low‐sodium diet for 7 days. On the day of experiment, rats were anaesthetized and received either a sodium load of 1.5 mmol/kg as 3 mol/L saline or an equivalent volume of an iso‐osmotic urea solution by direct gastric puncture. Blood was sampled and livers were harvested at 0 and 30 min after sodium or urea administration. Angiotensin‐converting enzyme was measured in serum and tissue homogen‐ates by generation of histidyl‐leucine.3. In the liver, ACE activity decreased from control after both sodium (P < 0.005) and urea (P < 0.025) administration. The decrease was greater in the group that received saline compared with rats that received urea (P < 0.05). Serum ACE decreased in response to urea (P < 0.025) but not sodium administration.4. We conclude that stimulation of the gastric sodium monitor results in a decrease in ACE activity in the liver. This decrease in ACE activity may be contributory to the decrease in AngII synthesis.
STIMULATION OF GASTRIC OSMORECEPTORS BUT NOT THE SODIUM MONITOR INCREASES RENAL ANGIOTENSIN‐CONVERTING ENZYME ACTIVITY
Authors: Ye VZC , Duggan KA 
Published: June 2007

SUMMARY1. Stimulation of the gastric sodium monitor has been reported to cause a decrease in renal nerve activity and also a decrease in plasma renin activity in renal venous blood. This suggests that changes in sympathetic nerve activity and in the intrarenal renin‐angiotensin system may mediate the natriuresis that occurs following gastric sodium administration. In the present study we sought to determine whether gastric sodium administration also modulates angiotensin‐converting enzyme (ACE) activity in the kidney.2. Male Sprague‐Dawley rats were equilibrated on a low‐sodium (0.008%) diet for 7 days. On the day of the experiment, rats were anaesthetized and kidneys were harvested and immediately snap frozen at 0 and 60min after intragastric administration of a saline load (1.5 mmol/kg as 3 mol/L saline) or an equivalent volume of iso‐osmotic urea (5.95%). Angiotensin‐converting enzyme activity was determined by incubation of kidney homogenates with hippuryl‐histidyl‐leucine and fluoro‐metric assay of the histidyl‐leucine generated.3. Angiotensin‐converting enzyme activity in the kidney increased in response to the intragastric administration of both sodium chloride and urea. Angiotensin‐converting enzyme activity increased significantly from control levels (189.9 ± 24.3 nmol/min per g protein) by 60 min in both NaCl‐ and urea‐treated groups (492.3 ± 27.3 and 468.6 ± 28.7 nmol/min per g protein, respectively; P < 0.0005).4. We conclude that instillation of sodium chloride or iso‐osmotic urea into the stomach increases ACE activity in the kidney. The results of the present study suggest that this effect is due to changes in osmolality rather than stimulation of the gastric sodium monitor.
EFFECTS OF ADRENALINE INFUSION ON PLASMA LIPIDS AND NORADRENALINE LEVELS IN RABBITS WITH ADRIAMYCIN‐INDUCED CARDIOMYOPATHY
Authors: Minatoguchi Shinya , Uno Yoshihiro , Seishima Mitsuru , Koshiji Masatoshi , Kakami Masao , Yokoyama Hitomi , Ito Hiroyasu , Fujiwara Hisayoshi 
Published: June 2007

SUMMARY1. We investigated the acute effects of adrenaline infusion on plasma lipid levels in vehicle‐ and adriamycin‐treated rabbits. Lipids were measured before and 30 and 60 min after the commencement of continuous intravenous administration of adrenaline (0.06 |xg/kg per min) or saline in pentobarbital‐anaesthetized rabbits.2. Adrenaline infusion significantly increased plasma free fatty acid (P < 0.05) and noradrenaline (NA) levels (P < 0.05) in vehicle‐treated control rabbits, but not in adriamycin‐treated rabbits. However, adrenaline had no effect on plasma total cholesterol, free cholesterol, high‐density lipoprotein‐cholesterol, triglyceride or phospholipid levels.3. Pretreatment with propranolol almost completely inhibited increased plasma free fatty acid and NA levels associated with adrenaline infusion, suggesting that adrenaline increases plasma free fatty acid and NA levels via the stimulation of p‐adreno‐ceptors in vehicle‐treated rabbits.4. It is suggested that both the production of plasma free fatty acids and the release of NA via the activation of β‐adrenoceptors is reduced in rabbits with adriamycin‐induced cardiomyopathy. This may be related to the down‐regulation of β‐adrenoceptors caused by elevated plasma NA levels induced by cardiac failure.
EFFECTS OF SARAFOTOXIN S6c ON RENAL HAEMODYNAMICS AND URINE FORMATION IN ANAESTHETIZED DOGS
Authors: Matsuo Gen , Matsumura Yasuo , Tadano Kiyoshi , Hashimoto Takashi , Morimoto Shiro 
Published: June 2007

SUMMARY1. The effects of sarafotoxin S6c (S6c), a selective endothelin ETB receptor agonist, on renal haemodynamics and urine formation were examined in anaesthetized dogs.2. Intrarenal arterial infusion of S6c at a rate of 1 or 5 ng/kg per min produced a transient increase in renal blood flow (RBF), with no change in systemic blood pressure and heart rate; RBF then decreased gradually to below the basal value. There were significant and dose‐dependent increases in urine flow and free water clearance and decreases in urine osmolality during S6c infusion, whereas urinary excretion of sodium and glomerular filtration rate (GFR) remained unchanged. Simultaneously, S6c administration elicited a marked increase in urinary excretion of nitric oxide (NO) metabolites, N02− and N03− (UNO*V).3. In dogs simultaneously administered S6c (5 ng/kg per min) and iVG‐nitro‐L‐arginine (NOARG; 40 (jig/kg per min), a NO synthase inhibitor, the renal vasodilator effect of S6c was abolished and marked reductions in RBF and GFR were observed. The S6c‐induced diuretic action was not affected by NOARG. In the presence of NOARG, there was a small amount of UNOxV at the basal level and the administration of S6c did not increase UNOxV.4. These results suggest that an intrarenal arterial infusion of S6c enhances the production of NO in the kidney and that this enhancement contributes to the peptide‐induced renal vasodilation. In contrast, it is unlikely that S6c‐induced water diuresis is related to NO production stimulated by this peptide.
COMPETITION OF ADENINE NUCLEOTIDES FOR A l,3‐[3H]‐DIPROPYL‐8‐CYCLOPENTYLXANTHINE BINDING SITE IN RAT VAS DEFERENS
Authors: Smith Andrew D. , Cheek Dennis J. , Buxton Iain LO , Westfall David P. 
Published: June 2007

SUMMARY1. The binding of l,3‐[3H]‐dipropyl‐8‐cyclopentylxanthine ([3H]‐DPCPX), a specific adenosine Ai receptor antagonist, was examined in rat vas deferens membrane preparations using radioligand binding techniques.2. l,3‐[3H]‐Dipropyl‐8‐cyclopentylxanthine bound to these preparations with a KD of 1.07 ± 0.14 nmol/L (n = 6). The density of [3H]‐DPCPX binding sites was 133.38 ± 5.57 fmol/mg protein.3. Computer analysis indicated that nucleosides competed for [3H]‐DPCPX binding at two distinct sites. The rank order of potency at the higher affinity site corresponded to R‐phenyliso‐propyladenosine (R‐PIA) 2‐chloroadenosine (2‐CI ADO) cyclopentyladenosine (CPA) N‐ethylcarboxamidoadenosine (NECA)>s‐phenylisopropyladenosine (s‐PIA). Kj values were in the low nmol/L range. The rank order of nucleoside potency at the lower affinity site corresponded to R‐PIA CPA NECA>=2‐ClADO> S‐PIA. Ki values were in the low μmol/L range.4. Nucleotides competed for [3H]‐DPCPX binding at a single site only. The rank order of potency at this site corresponded to a,β‐methylene ATP βγ‐methylene ATP = ATP. Ki values were in the high |xmol/L range. This site seemed to correspond with one of the two binding sites predicted by nucleoside competition binding.5. The ATP‐regenerating compound myokinase did not significantly change the competition curve for ATP, indicating that the competition for [3H]‐DPCPX binding observed in the presence of ATP was due to an effect of ATP per se and not to an action of a degradation product.6. The results demonstrate that in rat vasa deferentia there exist two distinct binding sites for [3H]‐DPCPX. One of these sites binds only nucleosides and may represent an adenosine Ai receptor, as usually defined. The other site binds both nucleosides and nucleotides and may represent an atypical adenosine A1 receptor, an atypical P2 or a P3 purinoceptor.
LONG‐TERM EFFECT OF MANIDIPINE ON RENAL FUNCTION AND STRUCTURE IN UNINEPHRECTOMIZED SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Fujimaki Michitaka , Nagase Mitsumasa , Uchida Shunya 
Published: June 2007

SUMMARY1. Long‐term effects of manidipine hydrochloride (MAN), a calcium channel blocker, were examined in three groups of spontaneously hypertensive rats (SHR). Group 1 was given uninephrectomy (UNX) and MAN treatment, group 2 was given UNX and was not treated with MAN and group 3 was given neither UNX nor MAN treatment2. At week 15 after UNX, inulin clearance in group 1 rats decreased compared with rats in groups 2 and 3, but remained at the same level at week 40, when the level in group 2 rats declined below that in rats in groups 1 and 3.3. Glomerular and tubulointerstitial lesions did not differ at week 15 after UNX among the three groups, whereas at week 40 both were advanced in the order of groups 2,1 and 3.4. Proteinuria did not differ between rats in groups 1 and 2 over the experimental period.5. At week 15, the kidney weights of group 1 rats were greater than those of group 2 rats, indicating more prominent tubular hypertrophy in the former group. This was confirmed by morphometry of the proximal tubuli. In contrast, the glomerular volumes of rats in groups 1 and 2 were enlarged compared with that of rats in group 3, with no difference between the former two groups.6. The findings suggest that MAN exerts renoprotective effects in SHR, both with regard to function and morphology. An effect on glomerular haemody naniics was considered to more likely be the mechanism underlying the renoprotective effect of MAN rather than that of a lowering of systemic blood pressure.7. Augmented tubular hypertrophy after MAN treatment was an unexpected finding of the present study and the biological significance of this finding remains to be explored.
THE EUGLYCAEMIC HYPERINSULINAEMIC CLAMP: AN EVALUATION OF CURRENT METHODOLOGY
Authors: Morris Andrew D. , Ueda Shinchiro , Petrie John R. , Connell John MC , Elliott Henry L. , Donnelly Richard 
Published: June 2007

SUMMARY1. The recognition of the role of insulin resistance in disease states and the recent development of new drugs that modify insulin‐dependent metabolism has led to increased use of the euglycaemic hyperinsulinaemic clamp to measure in vivo insulin sensitivity, but several key aspects of the technique are poorly documented in the literature.2. We have evaluated the reproducibility and intersubject variation of measurements of insulin sensitivity in groups of insulin‐sensitive and insulin‐resistant subjects and assessed the effects of hand warming on haemodynamic and metabolic responses.3. Subjects participated in one of two protocols: (i) 18 healthy male volunteers and 18 patients with hypertension and glucose intolerance were clamped on two occasions, 1 week apart with measurements of insulin sensitivity (M) derived after 120 and 180 min of hyperinsulinaemia; and (ii) six healthy volunteers were clamped on one occasion with simultaneous sampling of antecubital and ‘arterialized’ (dorsal hand) venous blood for comparison of plasma glucose concentrations and oxygen saturation and a further six volunteers were clamped on two occasions with and without the use of hand warming.4. Measurements of M derived after 120 min (M120) and 180 min (M180) of hyperinsulinaemia were reproducible: the coefficients of repeatability (mg/kg per min) of M120 and M180 were 1.0 and 0.9 for volunteers and 1.0 and 1.0 for the patient group, respectively. The intersubject variation in insulin stimulus was high: coefficients of variation for M180 were 22% for volunteers compared with 38% for the patient group. In volunteers compared with the patient group, hand warming significantly increased venous oxygen saturations (95 ± 2 vs 79 ± 18%, respectively) and glucose concentrations (5.2 ± 0.2 vs 4.5 ± 0.4 mmol/L, respectively) and measurements of M were significantly higher using arterialized compared with antecubital venous blood. However, local hand warming was associated with systemic vasodilatation: blood pressure decreased (e.g. 6mmHg diastolic; P < 0.05) with a compensatory increase in heart rate (8 b.p.m.).5. In conclusion, clamps of 120 and 180 min duration yielded measurements of M that were reproducible. The technique is much more robust when used in the context of a crossover design because of the significant (20–40%) intersubject variation in M, even among apparently homogeneous male volunteers. Hand warming effectively arterializes venous blood and gives significantly higher M values, but induces systemic vasodilatation, which may confound measurements of M.
CHARACTERISTICS OF MEMBRANE TRANSPORT PROCESSES OF MACULA DENSA CELLS
Authors: Bell P Darwin , Lapointe Jean‐Yves 
Published: June 2007

SUMMARY1. Macula densa (MD) cells are located within the thick ascending limb (TAL) and have their apical surface in contact with tubular fluid and their basilar region in contact with the glomerulus. These cells sense changes in luminal fluid sodium chloride concentration ([NaCl]) and transmit signals resulting in changes in vascular resistance (tubuloglomerular feedback) and renin release.2. Current efforts have focused on understanding the cellular transport mechanisms of MD cells. Progress in this area has benefited from the use of the isolated perfused TAL‐glomerular preparation, which permits direct access to MD cells.3. Using microelectrodes to measure basolateral membrane potential (VBL) of MD cells, it was found that VBL was very sensitive to changes in luminal fluid [NaCl]. As [NaCl] was elevated from 20 to 150mmol/L, VBL was found to depolarize by over 30 mV.4. Basolateral membrane potential measurements were also used to identify an apical Na+: 2CI−: K+ cotransport pathway in MD cells that is the major pathway for NaCl entry into these cells.5. Other work identified a basolateral chloride channel that is presumed to be responsible for changes in VBL during alterations in luminal [NaCl]. This channel, which is the predominant conductance across the basolateral membrane, may be regulated by intracellular Ca2+ and cAMP.6. An apical Na+: H+ exchanger in MD cells was detected by measuring changes in intracellular pH using the fluorescent probe 2′,7′‐bis‐(2‐carboxyethyl)‐5(and‐6) carboxyfluorescein.7. Using patch‐clamp techniques, a high density of pH‐ and Ca2+‐sensitive K+ channels was observed at the apical membrane of MD cells.8. Other studies found that, at the normal physiological conditions prevailing at the end of the TAL (luminal [NaCl] of 20–60 mmol/L), reabsorption mediated by MD cells is very sensitive to changes in luminal [NaCl].
SOCIAL ISOLATION AFFECTS THE PATTERN OF CARDIOVASCULAR RESPONSES TO REPETITIVE ACOUSTIC STARTLE STIMULI
Authors: Blanc J. , Baudrie V. , Tulen J. , Ponchon P. , Gaudet E. , Elghozi JL 
Published: June 2007

SUMMARY1. The aim of this study was to investigate the cardiovascular responses to repetitive alerting stimuli in rats subjected to intermittent social isolation, in comparison with animals housed in pairs.SUMMARY.2 Ten male Wistar rats were implanted with a blood pressure (BP) telemetric system and enrolled in a randomized cross‐over study design. Rats were either isolated or housed in pairs for an 8 day period. At the end of each period, the animals were exposed to five acoustic stimuli (110 dB at 15 kHz, 80 ms after the impact, duration 700 ms) at 60 s intervals. For each stimulus, maximal BP and heart rate (HR) responses were calculated. BP variability was analysed in the frequency domain before the first stimulation using power spectral analysis.3. Isolated animals showed more faster breathing (1.71 vs 1.42 Hz in the paired condition). The 0.4 Hz zone of the systolic BP spectral power was not significantly affected by isolation (1.11 vs 0.85 mmHg2). BP and HR resting levels of isolated rats (121 mmHg for the systolic BP and 290 b.p.m.) were similar to those of animals housed in pairs (119 mmHg for the systolic BP and 279 b.p.m.).4. The first acoustic stimulus caused a brief rise in BP of a comparable amplitude in both conditions (24 ± 2 mmHg). A biphasic HR response was also observed, but the delayed bradycardia was more marked during isolation (37 vs 6 b.p.m. decrease). BP and HR levels were restored within 20 s.5. Interestingly, BP responses were progressively attenuated to become negligible at the fifth presentation (1 mmHg) in the isolated state, while during the paired state a substantial pressor response (13 mmHg) after each successive stimulus was maintained. Paired rats exhibited a constant HR profile across the trials, consisting in a slight HR increase (< 5 b.p.m.), concomitant with the BP elevation, followed by a delayed bradycardia (around 15 b.p.m.). HR profiles in the isolated condition differed markedly: HR rises increased in magnitude with the trial number, reaching 30 b.p.m. after the 5th trial.6. Spontaneous BP and HR increases, as observed throughout the experiment were quantitatively small (6 mmHg and < 10 b.p.m.) in the two conditions.7. These data indicate that isolation markedly affects the BP habituation profile to repetitive alerting stimuli. The BP response attenuation might unmask a tachycardic response. Alternatively, the amplified tachycardia following the latter stimuli might express sensitization to the conditioned fear resulting from isolation.
INVOLVEMENT OF NON‐NMDA AND NMDA RECEPTORS IN GLUTAMATE‐INDUCED PRESSOR OR DEPRESSOR RESPONSES OF THE PONS AND MEDULLA
Authors: Chen SY , Wu WC , Tseng CJ , Kuo JS , Chai CY 
Published: June 2007

SUMMARY1. Fifty‐five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito‐neally with urethane (400 mg/kg) and a‐chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded.2. In intact animals, monosodium L‐glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2‐amino‐5‐phosphonovaleric acid (D‐AP5, 0.025 mol/L, 50–100 nL), a competitive N‐methyl‐D‐aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D‐AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D‐AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM.3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro‐injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM.4. The above results suggest that the Glu‐induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu‐induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors.5. In both baroreceptor‐intact and ‐denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.