bluuebunny/crossref_metadata_2025_split huggingface dataset:
BLOOD PRESSURE AND LIFESPAN FOLLOWING BRIEF ACE INHIBITOR TREATMENT IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Harrap Stephen B. , Mirakian Christine , Datodi Shari R. , Lever Anthony F. 
Published: June 2007

SUMMARY1. Brief treatment with angiotensin‐converting enzyme (ACE) inhibitors in young spontaneously hypertensive rats (SHR) causes a reduction in blood pressure that persists into maturity. The lifetime effects of such treatment have not been studied.2. Nineteen male SHR were treated with either water (n= 9) or perindopril (3 mg/ kg per day) (n = 10) by daily gavage between 6 and 10 weeks of age and systolic blood pressure and bodyweight were measured each month until all animals died in old age.3. Following treatment the systolic blood pressure of SHR treated with perindopril remained consistently lower than control SHR until about 82 weeks of age. After this age the blood pressure of control SHR fell spontaneously so that smaller differences were observed between the two groups in the last 4 months of the study.4. Rats that received perindopril lived on average 1 month longer than control rats, but this difference was not statistically significant.5. Thus, brief ACE inhibition in early life in SHR ameliorated the hypertension throughout life.
EFFECTS OF HOE 140 ON SYSTEMIC DEPRESSOR RESPONSES TO BRADYKININ AND MESENTERIC VASCULAR REACTIVITY IN VIVO IN PREGNANT WISTAR‐KYOTO RATS
Authors: Chu Z. M. , Beilin L. J. 
Published: June 2007

SUMMARY1. To examine possible changes in vascular reactivity to exogenous bradykinin (BK) and the possible role of endogenous BK in reduced mesenteric vascular reactivity in pregnant rats. The authors studied the effects of Hoe 140 on systemic depressor responses to BK and on mesenteric vascular reactivity in in situ blood‐perfused mesenteric resistance vessels of 18–20 day pregnant and age‐matched non‐pregnant Wistar‐Kyoto rats (WKY).2. Mean intra‐arterial blood pressure (MBP) of pregnant rats was lower than non‐pregnant controls. Basal mesenteric perfusion pressure (BPP) was slightly, but not significantly, reduced in the pregnant group. Neither MBP nor BPP was significantly influenced by Hoe 140 (1 mg/kg. s.c.)3. Systemic depressor responses to BK (1–30 μg/kg, i.v.) were significantly increased in pregnant rats at 1 and 3 μg/kg. Hoe 140 completely abolished systemic depressor responses to BK in either pregnant or non‐pregnant animals.4. Mesenteric vascular responses to regional administration of noradrenaline, electrical stimulation of sympathetic nerve and angiotensin II were overall decreased in pregnant compared with non‐pregnant groups, but those responses were not significantly affected by Hoe 140 in either groups.5. The results suggested that although systemic depressor responses to exogenous BK were increased, endogenous BK does not contribute to decreased mesenteric vascular reactivity in vivo in pregnant WKY.
REPERFUSION FOLLOWING MYOCARDIAL ISCHAEMIA ENHANCES INOSITOL PHOSPHATE RELEASE IN THE ISOLATED PERFUSED RAT HEART
Authors: Anderson K. E. , Dart A. M. , Woodcock E. A. 
Published: June 2007

SUMMARY1. Global myocariial ischaemia (MI) for periods greater tan 5 min caused an inhibition of phosphatidylinositol specific phospholipase C (PtdIns‐PLC) activity.2. Two min reperfusion following a 20 min MI period, a time point associated with reperfusion‐induced arrhythmias, resulted in an activation of PtdIns‐PLC activity, dependent on endogenous noradrenaline and mediated via al‐adrenoceptors.3. This 2 min reperfusion response, in contrast to healthy myocardium, resulted in: (i) enhanced PtdIns‐PLC activity; (ii) increased sensitivity to endogenous noradrenaline; (iii) rapid increases in inositol(1,4,5)trisphosphate (Ins(1,4,5)P3); and (iv) PLC hydrolysis primarily of PtdIns(4,5)P2, such that the majority of InsP isomers derive from Ins(1,4,5)P3.4. Together, these data suggest a functional role for Ins(1,4,5)P3 under postischaemic reperfusion conditions, and provide a possible link between al‐adrenoceptor stimulation of the PtdIns turnover pathway and reperfusion injury.
HAEMODYNAMIC, RENAL AND HORMONAL RESPONSES TO ENALKIREN IN FOUR PATIENTS WITH POST‐SURGICAL OLIGURIA
Authors: Jackson B. , Liu G. , Perich R. B. , Paxton D. , McNicols L. , Gutteridge G. , Johnston C. I. 
Published: June 2007

SUMMARY1. The haemodynamic and hormonal responses of four patients with acute post‐surgical oliguria (urine output <0.5 mL/kg perh) were measured in response to the renin inhibitor enalkiren. Enalkiren was infused at 0.01 up to 0.1 mg/kg perh for up to 4h.2. Enalkiren infusion was associated with a progressive fall in blood pressure, clinically significant in three of the four patients. Systemic vascular resistance fell in proportion to blood pressure fall. Cardiac output and pulse rate remained unchanged. Effective renal plasma flow rose in all four cases (236 ± 19 to 327± 38). There was no change in urine flow rate, or urinary sodium excretion.3. Plasma renin activity (ng angiotensin I/mL perh) fell from 1.9 ± 0.5 to 0.02 ± 0.01 (P<0.04), plasma angiotensin II (pg/mL) fell from 104 ± 93 to 7.7 ± 1.5, and plasma aldosterone (ng/dL) fell from 32 ± 8 to 21 ± 9 (P= 0.03) at the highest infusion dose.4. Enalkiren inhibited plasma renin activity with reduced plasma angiotensin II and aldosterone concentrations. This was associated with vasodilation, reduced blood pressure and maintained cardiac output. There was no beneficial effect on renal function in these patients with post‐surgical oliguria.
EFFECT OF SEX‐RELATED CHANGES IN BLOOD PRESSURE AT ENTRY TO THE MRC TRIAL ON PREDICTION OF CARDIOVASCULAR RISK
Authors: Millar J. A. , Lever A. F. 
Published: June 2007

SUMMARY1. Using the MRC trial placebo group as the data source, we examined relationships between cardiovascular risk, gender, and blood pressure (BP) at screening, on entry to the trial, and after 3 months of follow up.2. Blood pressure on entry to the trial (162/98 mmHg) was significantly higher than at the second screening (154/95 mmHg) visit and at 3 months (144/91 mmHg). The entry BP was higher, and the changes from screening to entry and from entry to 3 months were greater in females. Females had a low cardiovascular risk, but because of the greater changes of BP at entry they were over‐represented at the top of the entry BP distribution, whereas males were over‐represented at the bottom. The result of these effects was that the relationship between cardiovascular risk and entry BP was shifted to the right and was flatter than the corresponding curves measured at screening or after 3 months of follow up.3. In consequence, the severity of hypertension in the trial population was overestimated from measurement of BP at entry, and the capacity of trial entry BP to predict cardiovascular risk was weakened.4. BP on entry to the MRC Trial was affected by a pressor effect that diminished the value of BP as a cardiovascular risk factor because it differentially affected sub‐populations by gender.
COMPARATIVE HAEMODYNAMIC EFFECTS OF VERAPAMIL, FLECAINIDE, AMIODARONE AND SOTALOL IN THE CONSCIOUS RABBIT
Authors: Twidale N. , Roberts‐Thomson P. , McRitchie R. J. , Chalmers J. P. 
Published: June 2007

SUMMARY1. The effect of intravenous boluses of verapamil (0.15 mg/kg), flecainide (2 mg/kg), amiodarone (5 mg/kg), and sotalol (l.5 mg/kg) on mean arterial pressure, heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), and peak rate of change of left ventricular pressure (LV dP/dt) were assessed in the conscious rabbit.2. All four drugs had negative inotropic effects: verapamil reduced peak LV dP/dt by 19±4% (mean±s.e.m.; P<0.01), flecainide by 27 ± 9% (P<0.001), amiodarone by 11 ± 2% (P<0.01) and sotalol by 13 ± 3% (P<0.01).3. The drugs had different effects on CO as a result of differences in their actions on peripheral blood vessels: verapamil and amiodarone produced, respectively, a 12 ± 4% (P<0.03) and 16 ± 6% (P<0.01) increase in CO associated with a substantial vasodilatory effect (TPR reduced 15 ± 7%[P<0.05] and 20 ± 5% [P<0.01], respectively). Flecainide caused only a small (6 ± 1%; P<0.01) increase in CO and sotalol had no effect on either CO or TPR.4. Bolus intravenous injections of verapamil, flecainide and amiodarone produced an increase in HR, while sotalol reduced HR by 10 ± 2% (P<0.01). The increase in HR and cardiac output seen with verapamil, flecainide and amiodarone was in part secondary to reflex increase in sympathetic tone and these changes were abolished after total cardiac autonomic blockade.5. The modest reduction in cardiac performance associated with sotalol was abolished by cardiac autonomic blockade, suggesting that the predominant effect of sotalol on contractility was mediated through its β‐adrenoceptor blocking effect.
RENIN GENE POLYMORPHISM ASSOCIATED WITH ALDOSTERONE RESPONSIVENESS TO THE RENINANGIOTENSIN SYSTEM IN PATIENTS WITH ALDOSTERONE‐PRODUCING ADENOMAS
Authors: Ballantine Donna M. , Klemm Shelley A. , Tunny Terry J. , Stowasser Michael , Gordon Richard D. 
Published: June 2007

SUMMARY1. Aldosterone levels in patients with unilateral aldosterone‐producing adenomas may be responsive or unresponsive to the renin‐angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia.2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals.3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness.4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension.
REMODELLING OF RESISTANCE ARTERIES BY TREATMENT WITH ENALAPRIL IN THE NEW ZEALAND GENETICALLY HYPERTENSIVE RAT
Authors: Ledingham J. M. , Phelan E. L. , Cross M. , Laverty R. , Millar J. A. 
Published: June 2007

SUMMARY1. New Zealand genetically hypertensive (GH) rats were treated with enalapril from the age of 4 to 10 weeks and the effects of treatment on the structure of mesenteric resistance arteries (MR A) was measured by use of stereological analysis of stained sections and by myograph techniques.2. Tail‐cuff blood pressure (BP) was measured weekly and intra‐arterial BP recorded just before MRA were either fixed by perfusion or mounted on a myograph.3. Stereological techniques (Cavalieri and optical dissector) were used to determine media and lumen volume, fraction of smooth muscle (SM) within the media and SM cell density. For MRA mounted on the myograph, lumen diameter, media thickness, active tension and active pressure were recorded.4. BP was significantly (P<0.0001) lowered by enalapril throughout the experiment. Intra‐arterial BP and left ventricular (LV) mass were also significantly lower in the enalapril treated GH rats (P<0.0001).5. Stereological measurements showed that enalapril treatment significantly (P<0.0001 reduced media volume by 50%, doubled lumen volume (P<0.0001)), reduced the fraction of SM in the media (P<0.04), and had no effect on the number of SM cell layers or on SM cell density.6. Myograph measurements showed a decrease in the ratio media thickness/lumen diameter which was accompanied by a decrease in maximum active tension and pressure development.7. In the GH rat early treatment with enalapril causes a true loss of medial tissue that is not simply due to rearrangement of existing media around an enlarged lumen.8. The reduction in media without changes in SM cell density or in the number of layers of SM cells supports the suggestion that angiotensin‐converting enzyme (ACEI) have an effect on cell matrix.
DIFFERENTIAL REGULATION OF UTERINE AND GLOMERULAR ANGIOTENSIN II RECEPTORS IN NORMAL AND HYPERTENSIVE PREGNANCY IN THE RAT
Authors: Yang Y. , Macdonald G. J. , Duggan K. A. 
Published: June 2007

SUMMARY1. In the non‐pregnant state uterine and glomerular angiotensin II (AII) receptors have been shown to regulate in a similar fashion. This study sought to determine whether such parallel regulation occurred during pregnancy. We also investigated the role of plasma AII in these changes.2. These studies were performed in Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR). The SHR has increased receptor number, increased sensitivity to infused AII and decreased plasma volume compared to the WKY. These features are also seen in pregnancy induced hypertension (PIH).3. Age matched female WKY and SHR were exposed to an appropriate breeder and sacrificed on day 14 of gestation. Plasma AII was measured by radio‐immunoassay. Uterine and glomerular receptor binding was determined by saturation analysis using 125I(Sar1,Ileu8)AII. Data were analysed using the program ligand.4. Uterine and glomerular AII receptors showed different patterns of regulation during pregnancy. The uterine AII receptor affinity decreased significantly in both strains at 14 days of gestation and receptor number also decreased significantly in WKY. In contrast, glomerular AII receptor affinity did not change significantly in either strain. Receptor numbers in the glomeruli increased significantly compared to their respective non‐pregnant controls.5. We conclude that the uterine and glomerular AII receptors do not regulate in a parallel fashion in pregnancy. Plasma AII concentration does not appear to be involved in the regulation of either uterine and glomerular receptor expression in pregnancy.
INOSITOL‐1,4,5‐TRISPHOSPHATE [INS(1,4,5)P3] AND INS(1,4,5)P3 RECEPTOR CONCENTRATIONS IN HEART TISSUES
Authors: Fitzgerald Melinda , Anderson Karen E. , Woodcock Elizabeth A. 
Published: June 2007

SUMMARY1. The isolation and culture of neonatal cardiomyocytes causes changes in the metabolism of inositol(1,4,5) trisphosphate (Ins(1,4,5)P3) from primarily dephosphorylation in the intact tissue to a combination of phosphorylation and dephosphorylation in the cultured cells (Woodcock et al. 1992).2. The content of Ins(1,4,5)P3 was found to be higher in intact heart tissue than in the isolated neonatal cells (10.9 ± 1.3 and 0.5 ± 0.1 pmol/mg tissue, mean ± s.e.m., n= 4, P<0.002, respectively).3. Despite this difference, Ins(1,4,5)P3 receptors in intact tissue and in isolated cells were not different in terms of affinity (8.0 ± 1.7 and 10.9 ± 1.6 nmol/L, n= 3, respectively) or concentration (143.3 ± 20.5 and 91.2 ± 16.0 fmol/mg protein, n = 3, respectively).4. Thus, while there appears to be a relationship between the tissue content of Ins(1,4,5)P3 and its metabolism, no relationship to the properties of Ins(1,4,5)P3 receptors could be demonstrated.
THE INFLUENCE OF CAPTOPRIL AND NALOXONE ON THE VALSALVA MANOEUVRE AND SYSTOLIC TIME INTERVALS IN HEALTHY VOLUNTEERS
Authors: Richter J. P. , Sommers De K. , Snyman J. R. 
Published: June 2007

SUMMARY1. The aim of the study was to ascertain whether the inhibition of the sympathetic nervous system by angiotensin‐converting enzyme (ACE) inhibitors is mediated by endogenous opioids. Naloxone was used to evaluate the effects of the latter on systolic time intervals (STI) and Valsalva manoeuvre‐induced blood pressure and heart rate changes.2. Baseline recordings were done in 12 healthy male volunteers and repeated 2h after oral administration of 75 mg of captopril and again after naloxone 0.4 mg/kg was administered intravenously over 10 min.3. After captopril there was a significant reduction in systolic (P<0.02) and mean blood pressure (P<0.04) without any changes in heart rate. Furthermore, captopril increased the Valsalva ratio (P<0.06) but did not influence inotropism as indicated by STI. Naloxone did not influence any of these findings.4. The changes in the Valsalva ratio after captopril were mediated by an increase in the maximum bradycardia in nine of the 12 subjects.5. The results indicate that endogenous opioids do not play a role in the putative sympatholytic effect of ACE inhibition.
SPONTANEOUS ENDOTHELIN PRODUCTION BY CIRCULATING MONONUCLEAR CELLS FROM PATIENTS WITH CHRONIC HEART FAILURE BUT NOT FROM NORMAL SUBJECTS
Authors: Krum Henry , Itescu Silviu 
Published: June 2007

SUMMARY1. Plasma endothelin‐1 (ET‐1) levels are increased in chronic heart failure (CHF). Because chronic immunologic activation occurs in CHF and mononuclear cells (MNC) are capable of ET‐1 production, the possible contribution of circulating MNC to the increased plasma ET‐1 levels in CHF patients was investigated.2. Unseparated MNC (107/mL) from eight CHF patients spontaneously produced ET‐1 (1.54 ± 0.37 pg/100 mL). After separation of MNC into monocytes (106/mL) and lymphocytes (107/mL) at ratios approximating those in the circulation, ET‐1 was spontaneously produced by CHF lymphocytes (0.81 ± 0.26 pg/100 mL), and after macrophage colony stimulating factor (MCSF) stimulation by CHF monocytes (0.56 ± 0.08 pg/100 mL). In contrast, there was neither spontaneous nor MCSF‐induced production of ET‐1 in six normal subjects.3. It was concluded that heightened ET‐1 production by MNC may contribute to increased plasma levels in CHF patients. Because unseparated MNC produced greater ET‐1 than lymphocytes and monocytes separately, contact between these MNC subtypes may be necessary for maximal ET‐1 production.
RESPONSE TO UNILATERAL ADRENALECTOMY FOR ALDOSTERONE‐PRODUCING ADENOMA: EFFECT OF POTASSIUM LEVELS AND ANGIOTENSIN RESPONSIVENESS
Authors: Stowasser M. , Klemm S. A. , Tunny T. J. , Storie W. J. , Rutherford J. C. , Gordon R. D. 
Published: June 2007

SUMMARY1. Normokalaemic primary aldosteronism (PA) masquerades as ‘essential hypertension', and 50% of patients with aldosterone‐producing adenoma (APA) are normokalaemic at presentation to this unit.2. Angiotensin‐responsive (AII‐R) APA is as common as angiotensin‐unresponsive (AII‐U) APA, and requires adrenal venous sampling for differentiation from bilateral adrenal hyperplasia (BAH).3. From 1981 to 1992, 55 patients with APA underwent unilateral adrenalectomy and were followed up for at least 12 months postoperatively. Hypertension was cured in 55% and improved in the remainder.4. Cure rate was lower (P<0.001) in males (11/32, 34%) vs females (19/23, 83%), lower (P<0.005) in patients over 45 years of age (13/33, 39%) vs those 45 years or younger (17/22, 77%), lower (P<0.05) in AII‐R APA (11/28, 39%) vs AII‐U APA (19/27, 70%) and tended to be lower (not significant) in normokalaemic APA (7/17, 41%) vs hypokalaemic APA (23/38, 61%).5. A higher proportion (P<0.001) of AII‐R APA patients were males (23/28, 82%) vs AII‐U APA (9/27, 33%), and a higher proportion were from the older age group (AII‐R APA 20/28, 71%vs AII‐U APA 13/27, 48%; P<0.05). Females with AII‐U APA who were hypokalaemic had a very high cure rate (16/17, 94%).6. Since unilateral adrenalectomy cures or improves blood pressure in normokalaemic and AII‐R as well as in hypokalaemic and AII‐U patients, all hypertensives should be screened for PA, and AII‐R APA differentiated from BAH in proven PA.
AGE‐RELATED CHANGES IN NEUROPEPTIDE Y CONTENT IN BRAIN AND PERIPHERAL TISSUES OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Pavia Jillian M. , Morris Margaret J. 
Published: June 2007

SUMMARY1. This study examined neuropeptide Y (NPY) concentrations in brain regions and peripheral tissues of young (3–4 months) and old (17–18 months) normotensive Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).2. Neuropeptide Y‐like immunoreactivity (NPY‐LI) was determined in kidney, adrenal, heart ventricles, atria and four brain regions, cerebral cortex, hypothalamus, ventrolateral medulla (VLM) and dorsomedial medulla containing the nucleus tractus solitarius (NTS), by radio‐immunoassay following acid extraction.3. Significant age‐related increases in organ weights were observed in atria, ventricle and kidney of both WKY and SHR (P<0.01). In order to take into account tissue hypertrophy, NPY‐LI data were analysed as pmol/g tissue as well as total pmol/tissue.4. At each age, similar NPY‐LI concentrations were observed in WKY and SHR in all brain regions. A significant age‐induced decrease in NPY‐LI concentration and total NPY content was found in the hypothalamus of both WKY and SHR (P<0.01).5. In the cardiac ventricle, decreases were observed in NPY‐LI concentration with ageing, and in SHR relative to WKY; however, no differences were observed in total NPY‐LI content. A significant age‐related increase in adrenal NPY‐LI concentration was observed. No age‐ or strain‐related alterations in atrial or renal NPY‐LI were detected, with the exception of an increase in total kidney NPY‐LI in WKY with ageing.6. Thus in the periphery, few changes in NPY‐LI were observed with genetic hypertension or with ageing. A significant reduction in hypothalamic NPY‐LI concentration occurred with age in both normotensive and hypertensive rats. Thus the previously reported age‐related reduction in NPY‐LI in the hypothalamus, an area where the peptide influences neuro‐endocrine responses and food and water ingestion, is not affected by hypertension.
ROLE OF CALCIUM‐ACTIVATED POTASSIUM CHANNELS IN THE RELAXATION OF TRACHEAL SMOOTH MUSCLES BY FORSKOLIN
Authors: Hiramatsu Tetsuo , Kume Hiroaki , Kotlikoff Michael I. , Takagi Kenzo 
Published: June 2007

SUMMARY1. The role of calcium‐activated potassium (KCa) channels in bronchodilation produced by a direct adenylyl cyclase activator, forskolin, was investigated. The involvement of intracellular cyclic AMP (cAMP) in the process was also examined.2. The isometric tension records from guinea‐pig tracheal smooth muscles indicated that application of charybdotoxin (ChTX), a selective inhibitor of large conductance KCa channels, led to a suppression of the relaxant effect of forskolin in the precontracted tissue by carbachol (CCh). However, the inhibitory action by ChTX had a much greater effect on the relaxation caused by isoproterenol than by forskolin.3. In contrast to the effect of ChTX, glybenclamide, a cromakalim‐sensitive K+ channel inhibitor and apamin, a small conductance KCa channel blocker, had no effects on the bronchodilation produced by forskolin.4. The effects of forskolin and nifedipine on tone produced by high K+ was compared. Concentration‐inhibition curves in guinea‐pig trachealis precontracted by 20 mmol/L K+ solution were similar for forskolin and nifedipine. Conversely, relaxation by forskolin was significantly diminished when tissues were contracted with 40 mmol/ L K+ solution, whereas nifedipine relaxations were unaffected.5. A single channel record from a cell‐attached patch in a porcine tracheal myocyte demonstrated that forskolin stimulates reversibly KCa channels without affecting the unitary amplitude.6. The results are consistent with forskolin‐induced relaxation occurring at least in part through the opening of ChTX‐sensitive KCa channels, by means of a cAMP‐dependent channel modulation. The lesser effect of ChTX on forskolin compared with isoproterenol‐induced relaxations suggests a tighter coupling between relaxation and channel opening by β‐adrenergic receptor stimulation, and is consistent with cAMP‐independent mechanisms of receptor‐channel coupling.
INCREASE IN HAEMATOCRIT IN BORDERLINE HYPERTENSIVE MEN
Authors: Siebers R. W. L. , Carter J. M. , Maling T. J. B. 
Published: June 2007

SUMMARY1. Haematologic parameters were measured in untreated borderline hypertensive (BHT) men, and weight and age matched with normotensive men to determine whether previously described increased haematocrit (Hct) in established hypertension is evident in borderline hypertension.2. Haematocrit was significantly increased in BHT men (mean 0.46, s.d. 0.032) compared with normotensive men (mean 0.43, s.d. 0.014) and correlated significantly with mean arterial pressure in this group (r = 0.67, P= 0.036) independent of weight.3. The correlation of blood pressure with Hct in BHT men supports the concept that increased Hct may contribute to increased blood viscosity and thus to raised arterial pressure.