bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECTS OF ATRIAL NATRIURETIC PEPTIDE ON PHENYLEPHRINE‐INDUCED RENIN RELEASE IN DOGS
Authors: Tomura Y. , Hisa H. , Satoh S.
Published: June 2007

1. The effect of atrial natriuretic peptide (ANP) on α‐adrenoceptor agonist‐induced renin release was examined in the de‐ennervated kidney of the anaesthetized dog pretreated with propranolol (1 mg/kg, intravenous).

2. Phenylephrine (50 ng/kg per min) infused into the renal artery increased the renal secretion rate of renin (RSR) without affecting systemic blood pressure or renal blood flow.

3. Although basal RSR was unaffected, the phenylephrine‐induced increase in RSR was abolished during intrarenal arterial infusion of ANP (10 ng/kg per min).

4. The results suggests that exogenously administered ANP could suppress α‐adrenoceptor‐mediated renin release in the dog.
SERUM ANGIOTENSIN CONVERTING ENZYME ACTIVITY AND PLASMA RENIN ACTIVITY IN EXPERIMENTAL MODELS OF RATS
Authors: Ibarra‐Rubio María Elena , Cruz Cristino , Tapia Edilia , Peña José Carlos , Pedraza‐Chaverrí José
Published: June 2007

1. Serum angiotensin converting enzyme activity (ACEA) and plasma renin activity (PRA) were determined in rats under different experimental conditions such as: nephrotic syndrome (NS), bilateral nephrectomy (BN), renovascular hypertension (RH), dehydration (DEH), anaesthesia (AN), low sodium diet (LSD) and high sodium diet (HSD), and injection with propranolol (PRO) and isoprenaline (ISO).

2. PRA increased in LSD, AN, NS, RH, DEH and IPT groups, and decreased in HSD, BN, and PRO groups. Serum ACEA did not change in RH, HSD, IPT, DEH, AN, and PRO groups, increased in NS group, and decreased in LSD and BN groups.

3. Serum ACEA changed in the opposite direction to PRA only in the LSD group. This finding suggests that ACE may limit the full expression of the reninangiotensin system in the LSD group, but not in the other groups.
β‐ADRENOCEPTOR MEDIATED SECRETION OF ACTIVE AND INACTIVE RENIN IN CONSCIOUS SHEEP
Authors: Al Kattan A. H. K. , Parker J. C. , Noble A. R.
Published: June 2007

1. β‐Adrenoceptor linked regulation of plasma active and inactive renin was investigated in sheep with indwelling artery, vein and bladder catheters. Concurrent changes in renal function were also monitored.

2. The β‐adrenoceptor agonist isoprenaline (bolus intravenous (i.v.) dose 0.5 mg/kg, 0.05 μg/kg per min) increased plasma active renin concentration within 15 min and reached a plateau increase of 306%. Initially plasma inactive renin remained unchanged but after 105 min it decreased.

3. The non‐selective β‐adrenoceptor antagonist propranolol (bolus i.v. dose 4 mg/kg, 40 μg/kg per min) did not significantly alter basal plasma active renin but selectively reduced inactive renin. The absence of any change in active renin may reflect the relatively low level of stress‐induced sympathetic activation in these conscious animals compared to equivalent studies carried out on human subjects.

4. Using the same dose schedules, propranolol completely blocked the isoprenaline‐induced increases in plasma active renin secretion even though it had no effect on the basal active renin levels.

5. The selective β1‐adrenoceptor antagonist atenolol (bolus i.v. dose 5 mg/kg) decreased basal plasma active renin by 24% (+135 min) but reduced plasma inactive renin by 75% compared to control.

6. Therefore, both a β‐adrenoceptor agonist (isoprenaline) and two β‐adrenoceptor antagonists (propranolol and atenolol) decreased plasma inactive renin concentration in conscious sheep.

7. These results are discussed in relation to the accompanying changes in arterial blood pressure and aspects of renal function.
RELATIONSHIP BETWEEN SYSTEMIC AND CORONARY VASCULAR RESPONSES TO DIGOXIN AND CONCURRENT DRUG THERAPY WITH VERAPAMIL/β‐ADRENOCEPTOR ANTAGONISTS IN HUMANS
Authors: Powell A. C. , Horowitz J. D. , Hasin Y. , Louis W. J.
Published: June 2007

1. In 24 patients who were undergoing coronary arteriography for the assessment of ischaemic heart disease, the relationship between the systemic and coronary vascular responses to acute intravenous digoxin administration (500 μg) and concurrent drug therapy with the calcium antagonist verapamil (group I) or a β‐adrenoceptor antagonist (group II) or neither of these agents (group III) was examined.

2. Systemic vascular resistance (SVR) tended to rise rapidly after digoxin injection in patients in groups II and III, and tended to decline initially in patients in group I; however, these differences were not statistically significant (variance ratio [VR] = 0.77).

3. No significant differences were observed in coronary vascular responses to acute digoxin administration between the three groups of patients (VR = 0.34).

4. For the entire group of 24 patients, no statistically significant digoxin‐induced effects on resistance could be demonstrated in either the systemic or coronary circulations, although in individual patients vasoconstrictor effects were observed.

5. We conclude that acute intravenous administration of digoxin does not consistently cause systemic or coronary vasoconstriction in patients with ischaemic heart disease. Variability in vasomotor responses to digoxin is not clearly related to concurrent drug therapy with verapamil or a β‐adrenoceptor antagonist. The observation that systemic vascular resistance tends to increase in the first few minutes after digoxin injection should be addressed in future studies.
DENSITY DEPENDENCE OF RESPIRATORY INPUT IMPEDANCE IN NORMAL SUBJECTS
Authors: Wouters E. F. M. , Lándsér F. J. , Polko A. H. , Visser B. F.
Published: June 2007

1. The forced oscillation technique is a non‐invasive and effort‐independent test used to characterize the mechanical impedance of the respiratory system. Total respiratory impedance was assessed from 4 to 52 Hz in 15 normal subjects breathing air and a helium‐oxygen mixture.

2. Breathing helium‐oxygen reduced respiratory resistance and its frequency dependence as well as respiratory reactance very significantly. Resonant frequency during He‐O2 breathing was 1.88 times higher than during air breathing.

3. It is concluded that by impedance measurement of the respiratory system in normal subjects a density‐dependent decrease of respiratory resistance due to decreased turbulence in the larger airways and a density‐dependent decrease in the inductive reactance can be found during breathing of low density gas mixtures.
ENZYME IMMUNOASSAY FOR METHIONINE‐ENKEPHALIN SULFOXIDE
Authors: Tiong George K. L. , Olley Jean E.
Published: June 2007

1. An immunoassay technique employing an enzyme‐labelled ligand was developed for the sulfoxide derivative of the opioid peptide methionine‐enkephalin (MOE).

2. The sensitivity of the enzyme immunoassay (EIA) was approximately twofold higher than that achieved in the radio‐immunoassay (RIA) using tritiated ligand. Cross‐reactivities of leucine‐enkephalin and β‐endorphin with the EIA were less than 0.1%, while that with Gly‐Gly‐Phe‐Met and oxidized Gly‐Gly‐Phe‐Met were 2.5% and 10.2%, respectively.

3. These results indicate that the EIA is a useful alternative to the RIA for the assay of small peptides.
PERTUSSIS TOXIN ATTENUATES ANGIOTENSIN II BUT NOT β‐ADRENOCEPTOR FACILITATION OF NORADRENALINE RELEASE FROM RAT KIDNEY CORTEX
Authors: Murphy Timothy V. , Majewski Henryk
Published: June 2007

1. Angiotensin II (AII; 0.01 and 0.1 μmol/L), angiotensin I (AI, 0.1 μmol/L) and the β‐adrenoceptor agonist isoprenaline (0.1 μmol/L) all facilitated the stimulation‐induced outflow of radioactivity from slices of rat kidney cortex incubated in [3H]‐noradrenaline.

2. Treatment of rats with pertussis toxin (25 and 50 μg/kg i.v.) to inactivate G‐proteins attenuated the facilitation caused by AII and AI, but not that caused by isoprenaline.

3. The hypothesis that isoprenaline enhances noradrenaline release by generating AII to activate facilitatory prejunctional AII receptors is not supported by the present study. The hypothesis predicts that pertussis toxin, by inactivating the G‐proteins associated with AII receptors, should have inhibited the facilitatory effect of isoprenaline. This did not occur.
RENAL AND MYOCARDIAL ADRENOCEPTORS IN STEROID CONTRACEPTIVE‐INDUCED HYPERTENSION IN RATS
Authors: Geraghty Dominic P. , Byrne K. Bruce , McPherson Grant A. , Burcher Elizabeth
Published: June 2007

1. Systolic blood pressure (SBP), bodyweight, organ weight, renal β‐adrenoceptor and myocardial β‐ and myocardial α1‐adrenoceptor characteristics were investigated in female Sprague‐Dawley rats after chronic subcutaneous (s.c.) administration of ethynyloestradiol (EE2, 0.2 μg/day), levonorgestrel (NG, 2.0 μg/day) separately and in combination (EE2/NG).

2. EE2 caused a sustained increase in SBP from 6 weeks (maximum at 14 weeks, +22 mmHg compared to control) which was accompanied by increased kidney and ventricle weight after 12 weeks. EE2/NG‐treated rats also demonstrated a gradual rise in SBP (maximum at 9 weeks, +18 mmHg compared with control) with renal and ventricular hypertrophy, but were normotensive by week 17 of treatment. In contrast, NG induced only transient SBP increases (maxima at 5 and 10 weeks, + 14 mmHg compared with control), unaccompanied by organ hypertrophy. Norethisterone (2 μg/day) also produced transient increases (weeks 6–8, + 13 mmHg) in SBP.

3. α1‐ and β‐adrenoceptors were investigated using [3H]‐prazosin and (‐)‐ [125I]‐iodocyanopindolol (ICYP), respectively. Myocardial α‐ and β‐adrenoceptors were unaffected by steroid contraceptive administration for up to 12 weeks. Renal β‐adrenoceptor affinity was markedly reduced in 12 week EE2‐treated rats (equilibrium dissociation constant, KD, 53±7 pmol/L) compared with controls (KD, 31±4 pmol/L), an effect which was prevented by co‐administration of NG (KD, 34±8 pmol/L). Renal β‐adrenoceptor number was not altered by any treatment.

4. The relatively late onset of organ hypertrophy and β‐adrenoceptor changes appear to result from, rather than cause, EE2‐induced hypertension.
SUBSENSITIVITY TO ATP AND SOME ANALOGUES IN PREPARATIONS OF RAT CAUDA EPIDIDYMIS AND VAS DEFERENS AFTER VASECTOMY
Authors: Ventura Sabatino , DeGaris Richard M. , Stead Cheryl K. , Pennefather Jocelyn N.
Published: June 2007

1. The effects of ATP and some of its more stable analogues have been examined upon preparations of epididymal and prostatic halves of vasa deferentia and of cauda epididymides from rats that had undergone vasectomy by medial transection of the vas deferens.

2. After unilateral vasectomy, the potencies of ATP, β, γ‐methylene ATP and 5’‐adenylylimidodiphosphate (AppNHp) in tissues ipsilateral to the vasectomy were decreased compared to tissues from the contralateral unoperated side of the animal.

3. Tissues from bilaterally vasectomized rats were less responsive to ATP when compared to tissues taken from sham‐operated rats.

4. Tissues taken from rats which had undergone vasovasostomies following unilateral vasectomy remained less responsive to these purines.

5. Responses of cauda epididymides and epididymal halves of vasa deferentia taken from unilaterally and bilaterally vasectomized rats to α, β‐methylene ATP usually did not differ from those of respective controls.

6. It is proposed that the subsensitivity which develops to ATP and some of its analogues on the epididymis and vas deferens following vasectomy may reflect increased breakdown, perhaps associated with changes in structural integrity of the tissues, rather than with the sympathetic denervation which is associated with vasectomy.
POSITIVE INOTROPIC AND VASOCONSTRICTOR RESPONSES TO 14β‐AMINOPREGNANE DERIVATIVES IN ISOLATED TISSUES FROM THE GUINEA‐PIG
Authors: Brown Lindsay
Published: June 2007

1. The objective of this study was to compare the positive inotropic and vasoconstrictor responses in guinea‐pig isolated tissues of the aminosteroid derivatives LND 623 and LND 796 and the cardiac glycoside ouabain.

2. Ouabain (‐ log EC50, 6.66±0.04, n= 11) was more potent as a positive inotropic agent on guinea‐pig right ventricular papillary muscles than either LND 623 (‐ log EC50, 6.26±0.08, n= 6) or LND 796 (‐ log EC50 5.66±0.05, n= 7). All compounds gave similar maximal increases in force of contraction. However, the ratio of the maximally effective concentration to the concentration giving 25% of the maximal response was approximately doubled for the aminosteroids compared with ouabain.

3. Ouabain (‐ log EC50 6.27), LND 623 (‐ log EC50 6.24) and LND 796 (‐ log EC50 5.43) produced slowly developing contractions of guinea‐pig thoracic aortic rings.

4. These results indicate that, while the aminopregnane derivatives and ouabain produce qualitatively similar results, the therapeutic range for the positive inotropic responses is greater for the aminosteroids.
FILTRATION FAILURE INDUCED BY pAMINOPHENOL IN RATS IS DUE TO RAISED INTRATUBULAR PRESSURE AND NOT CHANGES IN GLOMERULAR FUNCTION
Authors: Henry Mark A. , Harris Peter J. , Naughton Robert J. , Walker Lesley L. , Skinner Sandford L. , Tange John D.
Published: June 2007

1. The p‐aminophenol (pAP) model of tubular necrosis displays elevated tubular pressures equivalent to ‘stop‐flow’, with low glomerular filtration rate (GFR) but maintained blood flow and urine output. Renal function, micropuncture, and morphological studies were performed in anaesthetized rats to examine the causes of filtration failure.

2. At the height of pAP‐induced renal failure proximal tubular fluid reabsorption (Jv(a) was markedly reduced while proximal and distal free‐flow rates measured by tubular fluid collections during venting of the nephron were not significantly different from saline‐injected controls. Renal blood flow was maintained over the 4 h observation period despite extensive and selective proximal tubular necrosis. There was no temporal relationship between increased tubular pressure and cast formation.

3. Maintained blood and tubular fluid flow rates indicate that activation of tubuloglomerular feedback plays little or no part in pAP‐induced renal failure, which is apparently due to high fluid flow resistance in the region of the connecting tubule, late distal convolution or collecting ducts. Morphological appearances were consistent with compression of these segments.
THE ACTIONS OF TULOBUTEROL ON ISOLATED PREPARATIONS OF GRAVID HUMAN MYOMETRIUM
Authors: Ziccone S. P. , Paull J. D.
Published: June 2007

1. The effects of tulobuterol (Abbott 54173) on the contractile force developed by electrically stimulated strips of gravid (gestation 36–40 weeks) human uterine muscle were compared with those of isoprenaline and adrenalin.

2. Isoprenaline produced inhibition of electrically evoked contractions of myometrium from 12 of 17 women at concentrations at or below 1 μmol/L (range 0.001–1 μmol/L). It enhanced contractions at concentrations of 10–50 μmol/L. In tissues from the remaining five women isoprenaline produced neither inhibitory nor excitatory effects. Adrenalin (0.1–50 μmol/L) was found to enhance contractile force in a concentration‐dependent manner (EC50= 0.30 μmol/L).

3. In the presence of metoprolol (0.3 μmol/L), a selective antagonist at β1‐adrenoceptors, the isoprenaline concentration‐response relationship was shifted to the left, indicating that β‐adrenoceptors are present and that they mediate excitation in the human uterus.

4. In contrast tulobuterol (in neither the presence nor absence of metoprolol), in the same concentration range as isoprenaline and adrenalin, (0.001–50 μmol/L) was found to have no effect on the electrically evoked contraction of gravid human uterine muscle strips.
ABNORMALITIES OF RESISTANCE VESSEL STRUCTURE IN ESSENTIAL HYPERTENSION: ARE THESE IMPORTANT?
Authors: Mulvany M. J.
Published: June 2007

1. The relationship between essential hypertension and abnormalities of the proximal resistance vessels (small arteries) is reviewed, with particular emphasis on their structure.

2. There seems to be good evidence that the media: lumen ratio of these vessels is increased, and this may account for the increased pressor response.

3. Whether there is also growth is not clear, and it is possible that the altered structure is due to redistribution of existing cells.

4. Regardless of the basis for the altered structure, it appears that in essential hypertension the altered vascular structure is in itself sufficient to explain the increased peripheral resistance.

5. Paradoxically, the altered vascular structure does not seem to be the main determinant of blood pressure, but the altered vascular structure appears to allow it to perform its function in the most convenient fashion.

6. It is suggested that the interest in vascular structure lies in connection with therapy, for correction of blood pressure without correction of vascular structure will probably not prevent all the consequences of the disease.

7. Current therapies do not appear to be able, in the short‐term, to normalize vascular structure, indicating that there is a need to find other more specific ways of correcting vascular structure.
EFFECT OF LONG‐TERM TREATMENT WITH AN ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR ON THE RENIN‐ANGIOTENSIN SYSTEM IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Morishita Ryuichi , Higaki Jitsuo , Okunishi Hideki , Kawamoto Tatsuhiko , Ishii Kenji , Nakamura Fumiaki , Katahira Katsutoshi , Nagano Masahiro , Mikami Hiroshi , Miyazaki Mizuo , Ogihara Toshio
Published: June 2007

1. To obtain information on regulation of the brain renin–angiotensin system, the effect of long‐term administration of angiotensin‐converting enzyme (ACE) inhibitor on brain renin and angiotensinogen mRNA was studied.

2. Spirapril (3 mg/kg) was orally administered daily for 8 weeks to spontaneously hypertensive rats (SHR) from 12 weeks after birth. Renin and angiotensinogen mRNA in the brain and kidney were then quantitated by Northern blot analyses with [32P]‐labelled rat renin and angiotensinogen cDNA as hybridization probes. Plasma renin activity (PRA), angiotensin II (AII) concentration, plasma ACE activity and brain tissue ACE activity were also measured.

3. Compared with the control group, the Spirapril‐treated group had significantly lower blood pressure (P<0.01), significantly higher PRA (P<0.01), a not significantly different plasma AII concentration, and lower plasma and brain ACE activities (P<0.01). Interestingly, the brain renin and angiotensinogen mRNA levels of the two groups were similar, but the renal renin mRNA level was significantly higher in the Spirapril‐treated group (P<0.01).

4. These results indicate that the mRNA levels of brain renin and angiotensinogen were not affected by chronic ACE inhibition in the circulation and suggest that AII in the brain might not be affected by systemic ACE inhibition.
STRESS IN MICE INCREASES INTRINSIC PENTOBARBITONE SENSITIVITY BY A PREDOMINANTLY PHARMACODYNAMIC MECHANISM
Authors: Carmody John J. , Graham Garry G. , Ruigrok Marielle A.
Published: June 2007

1. Mice were swum for 3 min at room temperature.

2. After this stress ‘sleeping time’ in response to pentobarbitone was increased by over 70%.

3. Loss of ‘righting reflex’ occurred in these stressed animals at brain concentrations of pentobarbitone which were 40% lower than those needed for ‘sleep’ in the unstressed mice, indicating a true increase in sensitivity to the drug. ‘Waking’ (the return of the righting reflex) occurred at identical levels in both groups.

4. Kinetic analysis showed that the rates of absorption, elimination and transfer between plasma and brain were slower in the swum than in the unswum mice, probably because of the reduced body temperatures produced by the swimming.
EFFECTS OF RESPIRATION ON BLOOD PRESSURE AND HEART RATE VARIABILITY IN HUMANS
Authors: Elghozi Jean‐Luc , Laude Dominique , Girard Arlette
Published: June 2007

1. Non‐invasive continuous finger blood pressure (BP) measurement and a spectral technique based on the Fourier transform (FT) were recently combined to quantify short‐term fluctuations in haemodynamic variables.

2. Systolic BP (SBP) recording combined low frequency (LF, Mayer waves) plus high frequency (HF, respiratory) oscillations. The presence of HF oscillations of SBP probably reflects fluctuations in cardiac output. Heart rate (HR) also exhibited a combination of low and HF (respiratory) oscillations. The vagus nerve mediates the efferent control of the respiratory sinus arrhythmia (RSA).

3. During controlled breathing in a supine position, a change in SBP is associated with an opposite consequent change in HR. Respiratory sinus arrhythmia could therefore depend on the baroreceptor‐HR response to underlying SBP oscillations.

4. The fast regulation of R‐R interval by SBP through the baroreceptor‐HR reflex may explain why the respiratory variations in the diastolic BP are small.
CALCIUM‐CHANNEL BLOCKING AGENTS VERAPAMIL AND DILTIAZEM ARE INHIBITORS OF VASOPRESSIN‐INDUCED HUMAN PLATELET ACTIVATION
Authors: Anfossi Giovanni , Mularoni Elena , Massucco Paola , Cavalot Franco , Burzacca Serenella , Mattiello Luigi , Trovati Mariella
Published: June 2007

1. This study investigated the influences of calcium‐channel blocking agents verapamil and diltiazem on platelet responses induced by arginine vasopressin (AVP) and lysine vasopressin (LVP).

2. The substances inhibited platelet aggregation induced by both low and high AVP concentrations, LVP and adrenaline plus AVP. IC50 values of each drug are lower than those determined for ADP‐ and collagen‐elicited aggregation. Verapamil and diltiazem also decreased AVP‐induced thromboxane B2 synthesis.

3. Other series of experiments showed that the addition of ethyleneglycol‐bis‐(β‐amino‐ethyl ether) N, N'‐tetra‐acetic acid to platelet‐rich plasma samples also prevented the platelet response to vasopressin polypeptides.

4. Our data provide evidence that the effects of verapamil and diltiazem on vasopressin‐induced platelet responses may be directly related to inhibition of extracellular calcium entry.
DELAYED RECOVERY FROM NG‐NITRO‐L‐ARGININE IN THE CONSCIOUS SHEEP
Authors: Narkowic Christian K. , Vial Janet H. , Xu Xiao F.
Published: June 2007

1. In the chronic, awake, instrumented sheep model NG‐nitro‐L‐arginine (NOLA) an inhibitor of nitric oxide synthesis, injected at a dose of 40 mg/kg, produced a significant increase in systolic blood pressure (from 110±6 to 145±8 mmHg after 5 min) which persisted for at least 1 h but returned to baseline after 24 h.

2. When NOLA was repeated 1 and 4 days after the first injection, the blood pressure response was significantly attenuated, and at 1 day was no greater than the response to an equivalent volume of saline. The blood pressure response returned to the initial response with an 8 day interval between injections.

3. There was no significant blood pressure response to 100 mL of saline before the NOLA injection; however, 1 and 4 days after NOLA there was a significant rise in blood pressure.
RECOMBINANT HUMAN INTERLEUKIN‐6 ENHANCES THE ANTIPROLIFERATION AND DIFFERENTIATION INDUCING EFFECTS OF RETINOIC ACID IN HL‐60 HUMAN MYELOID LEUKAEMIC CELLS
Authors: Hassan H. T.
Published: June 2007

1. The effect of recombinant human interleukin‐6 on the antiproliferation and differentiation inducing actions of all‐trans retinoic acid in HL‐60 human myeloid leukaemia cells was studied in short‐term liquid suspension culture.

2. Interleukin‐6 alone showed no significant effect on HL‐60 human myeloid leukaemia cells.

3. The addition of interleukin‐6 to all‐trans retinoic acid‐treated cultures of HL‐60 human myeloid leukaemia cells significantly enhanced the desired antiproliferation effect of all‐trans retinoic acid.

4. The combination of interleukin‐6 with all‐trans retinoic acid reduced the doses of all‐trans retinoic acid required to induce the same differentiation of HL‐60 cells as single agent by between 1.7‐ and 4.8‐fold; that is, the efficacy of all‐trans retinoic acid in inducing the differentiation of human myeloid leukaemia HL‐60 cells was increased up to 4.8 times by its combination with interleukin‐6.

5. The combination of all‐trans retinoic acid and interleukin‐6 could provide an effective alternative therapy for elderly myeloid leukaemia patients.
ADRENALINE RELEASE BY THE HUMAN HEART
Authors: Esler Murray , Eisenhofer Graeme , Dart Anthony , Chin Jaye , Cox Helen , Lambert Gavin , Jennings Garry
Published: June 2007

1. Radiotracer methods were used to measure the rates of regional release of adrenaline and noradrenaline to plasma in humans.

2. No release of adrenaline could be detected from the heart, lungs, liver and kidneys at rest.

3. With the relatively mild activation of the cardiac sympathetic outflow associated with mental challenge and isometric exercise, cardiac adrenaline release remained undetectable.

4. During supine bicycle exercise, which increased cardiac noradrenaline release 10–20 fold, to a mean value of 128 ng/min, cardiac adrenaline release averaged 1.63 ng/min.

5. Whether neuronal adrenaline release of this degree in the heart is sufficient to facilitate noradrenaline release and to augment sympathetically mediated cardiac responses remains to be tested.
THE MACROPHAGE AS AN INITIATOR OF ATHEROSCLEROSIS
Authors: Campbell Julie H. , Campbell Gordon R.
Published: June 2007

1. Heparan sulfate proteoglycan in the basal lamina of smooth muscle cells is important in the maintenance of the ‘contractile’, high volume fraction of myofilaments (Vvmyo) phenotype. The mechanism by which this occurs may involve the continuous internalization of heparan sulfate by the smooth muscle cells themselves.

2. One macrophage can degrade all the heparan sulfate from three smooth muscle cells by the action of heparan sulfate‐degrading enzymes in their lysosomes, thus leaving none available for internalization by the smooth muscle cell until it has synthesized more, and leading to the induction of smooth muscle phenotypic change from a high Vvmyo to a low Vvmyo.

3. In this altered phenotype the smooth muscle cells proliferate in response to mitogens, synthesize large amounts of extracellular matrix and accumulate lipid, all characteristics of the smooth muscle cell in developing atheroma.
CHANGES IN CARDIAC ANGIOTENSIN CONVERTING ENZYME AFTER MYOCARDIAL INFARCTION AND HYPERTROPHY IN RATS
Authors: Johnston C. I. , Mooser V. , Sun Y. , Fabris B.
Published: June 2007

1. Cardiac angiotensin‐converting enzyme (ACE) is localized in high concentration in cardiac valves, coronary vessels, right and left atrium and right and left ventricle.

2. Cardiac ACE is functionally active in converting angiotension I to angiotensin II.

3. The level of cardiac ACE measured by radioinhibitor binding or by quantitative in vitro autoradiography was greatly increased after experimental myocardial infarction in the rat. The increase was greatest in the fibrous scar tissue of the free left ventricular wall infarct, but there were also significant increases in the ACE concentration in the four chambers of the heart.

4. Treatment with enalapril for 4 weeks following coronary ligation inhibited cardiac ACE, including the high levels found in the scar in the left ventricular free wall.

5. There was a close relationship between the systolic blood pressure and left ventricular mass in several models of experimental hypertension, despite varying degrees of activation of the renin–angiotensin system. However no relationship between the degree of left ventricular hypertrophy and changes in cardiac ACE could be determined.

6. Inhibition of cardiac ACE may contribute to the beneficial effect of ACE inhibitors in cardiac hypertrophy and remodelling, and may play a part in the cardioprotective role of ACE inhibitor.
IONIC MECHANISMS REGULATING SODIUM ENTRY INTO VASCULAR SMOOTH MUSCLE
Authors: Bobik Alex , Little Peter J. , Neylon Craig B.
Published: June 2007

1. Na+/H+ exchange, an ethylisopropylamiloride (EIPA)‐sensitive Na+ and HCO3‐ dependent system and a diisothio‐cyanatostilbenedisulphonic acid (DIDS)‐sensitive Na+ and HCO3‐ transporter, contribute to sodium influx and intracellular pH (pHi) regulation in vascular smooth muscle.

2. In cultured cells from the human internal mammary artery, Na+/H+ exchange and the EIPA‐sensitive Na+ and HCO3‐ dependent system contribute about 80% to basal sodium influx. The residual Na+ influx is both EIPA and DIDS‐insensitive.

3. Sodium influx via these mechanisms influences the ability of vascular smooth muscle to synthesize protein late in the G1 phase of the mitotic cell cycle. This, in turn, affects DNA biosysthesis.

4. These Na+ exchanges/transporters have the capability to facilitate the development of vascular hypertrophy in hypertension.
EFFECT OF PARATHYROIDECTOMY ON DEVELOPMENT OF HYPERTENSION AND ATRIAL RESPONSIVENESS IN SPONTANEOUS HYPERTENSIVE RATS
Authors: Schleiffer R. , Ghysel‐Burton J. , Finet M. , Gairard A.
Published: June 2007

1. In order to further clarify the relationships between parathyroid function and development of hypertension, the effects of parathyroidectomy (PTX) on blood pressure and on responsiveness of atria isolated from spontaneous hypertensive rats (SHR) were examined.

2. PTX was carried out in 6‐week‐old SHR and normotensive Wistar rats. The experiments were performed 2 weeks after surgery.

3. PTX reduced the plasma calcium concentration and decreased atrial calcium content in SHR. On the other hand, basal contractile force and beat frequency of isolated atria were higher in PTX SHR than in sham‐operated SHR. In response to cumulative addition of isoprenaline, atria from PTX SHR displayed diminished inotropic and chronotropic responses compared with sham‐operated SHR. Similar results were obtained in atria isolated from Wistar rats. When calcium sensitivity was studied in atria from Wistar rats, basal and isoprenaline‐induced maximum contractile forces were higher in PTX group than in the sham‐operated group. Nevertheless, basal and isoprenaline‐induced maximum contractile forces, determined at the respective plasma ionized calcium concentration of PTX and sham‐operated groups (0.83 and 1.22 mmol/L), were not significantly different.

4. Our results do not favour a role for alteration in atrial activity as a causal mechanism in delayed development of experimental genetic hypertension after parathyroidectomy.
INHIBITION OF CYCLIC GMP PHOSPHODIESTERASE BY XANTHINE DERIVATIVES RELAXES GUINEA‐PIG TRACHEALIS SMOOTH MUSCLE
Authors: Tanaka Hitoshi , Ogawa Kenji , Takagi Kenzo , Satake Tatsuo , Hidaka Hiroyoshi
Published: June 2007

1. For the purpose of clarifying the mechanism of the airways smooth muscle relaxant action of xanthines, cyclic guanosine monophosphate (GMP) phosphodiesterase (PDE) from guinea‐pig trachealis muscle was purified with diethylaminoethyl ether (DEAE) cellulose column chromatography.

2. Five 3‐alkylxanthines (3‐methylxanthine, 3‐ethylxanthine, 3‐n‐propylxanthine (enprofylline), 3‐n‐butylxanthine, and 3‐iso‐butylxanthine), and five 1‐methyl‐3‐alkylxanthines (1‐methyl‐3‐methyl‐xanthine (theophylline), 1‐methyl‐3‐ethylxanthine, 1‐methyl‐3‐n‐propylxanthine, 1‐methyl‐3‐n‐butyl‐xanthine, and 1‐methyl‐3‐iso‐butylxanthine (IBMX)) were compared in terms of purified cyclic GMP PDE inhibition. The relationship between the structure and inhibition of cyclic GMP PDE was studied.

3. The –log EC50 values for relaxation of spontaneous tone of isolated guinea‐pig trachealis preparations by the 3‐alkylxanthines and 1‐methyl‐3‐alkylxanthines were determined.

4. The five 1‐methyl‐3‐alkylxanthines were each more potent in relaxing isolated trachealis smooth muscle than the corresponding 3‐alkylxanthines. The 1‐methyl‐3‐alkylxanthines were also more potent than the corresponding 3‐alkylxanthines in their cyclic GMP PDE inhibitory effect. There was a strong positive correlation between the concentration of inhibitor which inhibited hydrolysis by 50% (IC50) values for cyclic GMP PDE inhibition by the xanthine derivatives and their EC50 values for trachealis muscle relaxation.

5. It is suggested that the mechanism by which xanthine derivatives relax trachealis smooth muscle involves inhibition of cyclic GMP PDE in addition to inhibition of cyclic adenosine monophosphate PDE.
FAILURE OF THE KETY‐SCHMIDT NITROUS OXIDE METHOD FOR DETERMINATION OF MYOCARDIAL BLOOD FLOW
Authors: Reid Michael A. , Mather Laurence E. , Runciman William B. , McLean Colin F.
Published: June 2007

1. The reliability of the Kety‐Schmidt nitrous oxide (N2O) blood–tissue equilibration method was examined in 50 studies of myocardial blood flow in seven conscious, unrestrained sheep using a newly developed carefully validated gas chromatographic assay for N2O.

2. In 10 studies the arterial and coronary sinus N2O blood concentration–time curves converged as expected at the end of the 10 min sampling period. In 14 studies they crossed over, and in 26 studies, the curves failed to converge.

3. A survey of the literature revealed that such results have been encountered previously but have not been accorded particular significance. An ultimate matching equilibrium between arterial and venous blood N2O concentration–time curves is, however, fundamental to the validity of the method.

4. The results indicate that the use of the Kety‐Schmidt method with N2O as the indicator gas is invalid as applied to the measurement of myocardial blood flow in this preparation.
SODIUM AND VOLUME DYSREGULATION AFTER APPARENTLY NORMAL PREGNANCY IS SUGGESTED BY ABNORMAL LEVELS OF ATRIAL NATRIURETIC PEPTIDE, RENIN AND ALDOSTERONE
Authors: Finn Wendy L. , Tunny Terry J. , Klemm Shelley A. , Jones Ian S. , De Voss Kerry , Gordon Richard D.
Published: June 2007

1. Plasma atrial natriuretic peptide (ANP), renin activity, aldosterone, sodium, potassium and serum total protein and albumin during and after 14 normal pregnancies were compared with age‐matched controls.

2. None developed toxaemia and all delivered healthy babies.

3. During pregnancy, plasma renin activity and aldosterone were significantly (P<0.01) higher and potassium, total protein and albumin significantly lower (P<0.01) than in controls, while ANP was not different from the control level.

4. At 6–13 weeks postpartum, a significant (P<0.01) suppression of renin and aldosterone was accompanied by significant (P<0.01) elevation of atrial natriuretic peptide when compared with controls.

5. The hormonal changes are consistent with ‘effective plasma volume’ reduction during pregnancy and persistent volume expansion after pregnancy, perhaps due to a renal glomerular lesion sustained late in pregnancy. In contrast, levels of potassium, total protein and albumin are consistent with haemodilution during pregnancy and its correction postpartum.

6. Measurements available in seven women 40–120 weeks postpartum showed normal renin and aldosterone levels in most, but ANP was still elevated.

7. Pregnancy may have a protracted effect on volume regulation.
URINARY STEROID PROFILES AND ALOCHOL‐RELATED BLOOD PRESSURE ELEVATION
Authors: Mori T. A. , Puddey I. B. , Wilkinson S. P. , Beilin L. J. , Vandongen R.
Published: June 2007

1. From an earlier cross‐sectional survey of 343 public servants, 15 pairs of non‐smoking teetotallers and heavy drinkers (alcohol intake more than 350 mL/week) were matched for age and adiposity and utilized for a case‐control study of the effects of alcohol on 11β‐hydroxysteroid dehydrogenase (11β‐OHSD) activity and blood pressure.

2. Two successive 24 h urine collections were analysed by radio‐immunoassay (RIA) for cortisol excretion, and for the cortisol and cortisone metabolites, tetrahydrocortisol (THC), allo‐tetrahydrocortisol (allo‐THC) and tetrahydrocortisone (THE), by capillary column gas chromatography.

3. Heavy drinkers had higher systolic and diastolic blood pressure (BP) than teetotallers (132.6 ± 2.5 vs 123.2 ± 1.3 and 78.7 ± 1.6 vs 71.7 ± 1.4, respectively; unpaired t‐test, P<0.01). Twenty‐four‐hour urinary sodium and cortisol excretion were similar in the two groups.

4. The THC plus allo‐THC: THE ratio was similar in drinkers and teetotallers (1.81 ± 0.20 vs 2.03 ± 0.20), consistent with no effect of alcohol on 11β‐OHSD activity. The ratio of THC to allo‐THC was increased in drinkers compared with teetotallers (1.49 ± 0.18 vs 1.05 ± 0.13; unpaired t‐test, P<0.05), consistent with either a decrease in 5α‐reductase activity or an increase in 5β‐reductase activity.

5. This study provides no evidence for alcohol‐related inhibition of 11β‐OHSD, despite substantially higher blood pressures in heavy drinkers compared to teetotallers. Such an effect is, therefore, unlikely to contribute significantly to the mechanism of alcohol‐related hypertension. The increase in the THC: allo‐THC ratio is consistent with a redox effect on steroid metabolism.
AUTORADIOGRAPHIC LOCALIZATION OF ANGIOTENSIN‐CONVERTING ENZYME AND ANGIOTENSIN II BINDING SITES IN EARLY ATHEROMA‐LIKE LESIONS IN RABBIT ARTERIES
Authors: Zambetis‐Bellesis Maria , Dusting Gregory J. , Mendelsohn Frederick A. O. , Richardson Karen
Published: June 2007

1. Early atheroma‐like lesions in rabbits are associated with increased sensitivity to serotonin. The localization and distribution of angiotensin‐converting enzyme (ACE) and angiotensin II (AII) binding sites has been studied in these developing lesions by quantitative in vitro autoradiography.

2. In sham‐operated control vessels, ACE was localized predominantly to intimal and adventitial sites, whereas in lesioned arteries the level of ACE detected in these regions was significantly reduced.

3. In control vessels AII receptor binding was distributed largely in the outer media, whereas in lesioned vessels AII receptor binding was dispersed throughout the media with the highest levels of binding in the outer media.

4. There was a significant amount of binding associated with ACE and with AII receptors in the extra‐adventitial inflammatory tissue of lesioned arteries.

5. Apparent loss of ACE from intimal and adventitial sites may be a consequence of tissue remodelling and cellular proliferation, while the appearance of ACE in abnormal sites could play a role in AII production by the vessel wall. The role of ACE and AII in the developing atheroma‐like lesions needs to be investigated further.
EFFECT OF ANGIOTENSIN‐CONVERTING ENZYME INHIBITION ON RENAL NOREPINEPHRINE SPILLOVER RATE AND BAROREFLEX RESPONSES IN CONSCIOUS RABBITS
Authors: Noshiro Takao , Way Diana , McGrath Barry P.
Published: June 2007

1. To evaluate the effects of angiotensin‐converting enzyme (ACE) inhibition on sympathetic nerve activity, renal and total norepinephrine (NE) spillover rates were examined under control conditions and during enalaprilat infusion at rest and in response to sodium nitroprusside (SNP)‐induced hypotension.

2. Resting renal and total NE spillover rate during enalaprilat infusion were similar to control values.

3. During SNP infusion at 10 μg/kg per min, renal NE spillover rate increased by 26% in enalaprilat‐treated group and by 39% in controls, in response to falls in mean arterial pressure (MAP) of 25 and 19% respectively.

4. During sympathetic stimulation induced by SNP, total NE spillover rate was significantly increased in both groups, but the 50% (s.e.m. = 12) increase in the enalaprilat‐treated group was less (P<0.05) than the 97% (s.e.m. = 16) change observed in controls.

5. Enalaprilat treatment resulted in a higher renal to total NE spillover ratio (P<0.05). The ratio fell in parallel in both groups during SNP‐induced hypotension.

6. This study indicates that the sympathetic nervous system interacts dynamically with the renin‐angiotensin system during hypotensive stimulation but this occurs predominantly at sites other than the kidney.
L‐NITROARGININE INCREASES BLOOD PRESSURE IN THE RAT
Authors: Kobayashi Yuta , Ikeda Katsumi , Shinozuka Kazumasa , Nara Yasuo , Yamori Yukio , Hattori Keisuke
Published: June 2007

1. Effects of administration of NG‐nitro‐L‐arginine (NO2Arg), a guanidino nitroarginine derivative, for 1 week on blood pressure and some vascular responses of rats were studied.

2. A significant rise of the systolic blood pressure was observed after the administration of NO2Arg with food (0.023% in weight, about 2.8 mg of NO2Arg per rat per day). Relaxation by acetylcholine decreased markedly in ring preparations of the thoracic aorta of NO2Arg‐treated rats. However, glyceryltrinitrate‐induced relaxation was not reduced after NO2Arg administration, suggesting that NO2Arg administration specifically inhibited endothelium‐dependent relaxation.

3. An increase of blood pressure may be because oral administration of NO2Arg inhibited endothelium‐dependent relaxation in vivo suggesting that the release of EDRF is important in physiological control of blood pressure.
EFFECT OF GONADOTROPINS AND PREGNANCY ON PRORENIN AND RENIN IN THE RAT
Authors: Nielsen Arne Høj , Hagemann Arne , Poulsen Knud
Published: June 2007

1. Stimulation of adult female rats with pregnant mare serum gonadotropin (PMSG) and human chorion gonadotropin (hCG) increased active plasma renin about two‐fold, but caused only a slight increase of plasma prorenin. The concentrations of active renin and prorenin in the ovaries, and active renin in the uterus all increased about two‐fold 2 days after stimulation with PMSG. The prorenin in the uterus was below detection in unstimulated rats and did not change consistently after PMSG.

2. Active renin and prorenin in plasma were unchanged in relation to pregnancy, except for a slight decrease of prorenin in the third trimester. In the first and third trimester the concentration in the ovaries of active renin and prorenin was decreased to about one‐third of that in normal female rats. In contrast active renin in the uterus was increased about two‐fold in the first trimester, whereas prorenin did not change consistently.

3. Our results confirm that gonadotropins and pregnancy affect the renin–angiotensin system in rats. However, the changes in the plasma seem to be much smaller than those previously reported in humans. Accordingly, our results do not support a systemic role of prorenin for reproduction in the rat.
DILTIAZEM AND VERAPAMIL LOWER BLOOD PRESSURE IN THE UNANAESTHETIZED RAT THROUGH CNS MECHANISMS INVOLVING ENDOGENOUS OPIOIDS
Authors: Rabkin Simon W.
Published: June 2007

1. To evaluate and compare the effects of the calcium channel blockers, diltiazem and verapamil, on CNS modulation of blood pressure, unanaesthetized and unrestrained rats with catheters previously inserted into the lateral cerebral ventricle and femoral artery received intra‐cerebroventricular (i.c.v.) administration of diltiazem or verapamil, 10 or 50 μg/kg, or their diluent.

2. Diltiazem, at both 10 and 50 μg/kg i.c.v., produced significant (P<0.05) decreases in systolic and diastolic blood pressure and heart rate. Verapamil, at 50 μg/kg but not at 10 μg/kg i.c.v., produced a significant (P<0.05) decrease in blood pressure, while both doses significantly (P<0.05) decreased heart rate.

3. To examine the endogenous opioid systems as potential modulators of the effects of these calcium antagonists, the mu opioid antagonist naloxone, 20 μg/kg, was administered i.c.v. either before or after each calcium antagonist. Naloxone reversed and prevented the reduction in blood pressure produced by both agents. The decrease in heart rate produced by verapamil but not diltiazem was reversed by naloxone.

4. The results suggest that: (1) calcium channels in neuron membranes in the CNS play a role in blood pressure regulation; (2) at least part of the blood pressure reduction produced by calcium blockers may be effected in the CNS; and (3) central opioid mechanisms modulate part of the action of the calcium antagonists verapamil and diltiazem on blood pressure.
THE EFFECT OF AZUMOLENE ON HYPERCONTRACTILITY AND SARCOPLASMIC RETICULUM CA2+‐DEPENDENT ATPASE ACTIVITY OF MALIGNANT HYPERPYREXIASUSCEPTIBLE PORCINE SKELETAL MUSCLE
Authors: Foster P. S. , Hopkinson K. C. , Payne N. , Denborough M. A.
Published: June 2007

1. Azumolene sodium is a new water‐soluble derivative of dantrolene sodium that also acts as a skeletal‐muscle relaxant.

2. Azumolene (6 μmol/L) inhibited the hypercontractility induced separately by 3% halothane, 2 mmol/L caffeine and 80 mmol/L potassium chloride in isolated malignant hyperpyrexia (MH)‐susceptible muscle. Azumolene was equipotent with dantrolene in inhibiting the abnormal responses.

3. Like dantrolene, azumolene (6 μmol/L) not only prevented but reversed the abnormal contractures induced by halothane and caffeine. Contracture responses to caffeine were also modified by azumolene in control preparations.

4. In the presence of maximal effective concentrations of dantrolene, azumolene failed to further relax caffeine‐induced contractures, and the converse was also true. This was observed in both MH‐susceptible and control preparations.

5. Sarcoplasmic reticulum Ca2+‐dependent ATPase activity from MH‐susceptible and control muscle was not affected by azumolene.

6. Like dantrolene, azumolene may inhibit Ca2+ release directly from the sarcoplasmic reticulum and be of therapeutic value for the treatment of MH.
EFFECTS OF TORASEMIDE ON RENAL HAEMODYNAMICS AND FUNCTION IN ANAESTHETIZED DOGS
Authors: Uchida T. , Hayashi K. , Suzuki Y. , Matsumura Y.
Published: June 2007

1. We examined the effects of torasemide (0.3 and 1 mg/kg i.v.) on renal haemodynamics and function employing renal clearance and stop‐flow techniques in anaesthetized dogs and compared these with furosemide (1 and 3 mg/kg i.v.).

2. Torasemide and furosemide did not influence renal haemodynamics, in the renal clearance study, but caused a dose‐related and significant increase in urine flow and urinary excretion of sodium and potassium. Torasemide and furosemide increased fractional excretion of sodium in the distal tubules with a relatively small increase in the fractional excretion of lithium (index of sodium excretion at the proximal tubules, FELi). The diuretic profile of torasemide was of long duration, compared with that of furosemide.

3. Torasemide and furosemide inhibited sodium reabsorption at the distal portion of the tubules in the stop‐flow study.

4. It is suggested from these results, that the main diuretic site of action of torasemide is the ascending limb of the loop of Henlé.
EFFECT OF DELAPRIL ON THE VASCULAR ANGIOTENSIN II RELEASE IN ISOLATED HIND LEGS OF THE SPONTANEOUSLY HYPERTENSIVE RAT: EVIDENCE FOR POTENTIAL RELEVANCE OF VASCULAR ANGIOTENSIN II TO THE MAINTENANCE OF HYPERTENSION
Authors: Mizuno Kenji , Tani Makio , Niimura Susumu , Fukuchi Soitsu
Published: June 2007

1. In view of a recent interesting hypothesis that the vascular renin‐angiotensin system (RAS) plays an important role in the maintenance of hypertension, we examined the effect of delapril (DP), a newly developed angiotensin converting enzyme inhibitor (ACEI), on angiotensin II (Ang II) release from isolated perfused hind legs of spontaneously hypertensive rats (SHR) in comparison with normotensive rats of Wistar‐Kyoto strain (WKY).

2. Male SHR and WKY were given DP orally (10 mg/kg per day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen‐free Krebs‐Ringer solution, and Ang II released into the perfusate was determined directly by extraction with Sep‐Pak C18 cartridges connected to the perfusion system.

3. Delapril produced a sustained antihypertensive action in SHR but not in WKY. The spontaneous release of Ang II in SHR was 112.9±17.6 pg during the first 30 min of perfusion, which was somewhat greater than that in WKY (96.5±9.8 pg). An active metabolite of DP, delapril diacid (DPD), when added to the perfusion medium, suppressed the Ang II release in a dose‐dependent manner in the two strains. Oral pretreatment of DP for 2 weeks suppressed the Ang II release by 60% in WKY and more pronouncedly by 73% in SHR.

4. These results suggest the presence of a functional RAS in vascular tissues which contributes to the maintenance of vascular tone of SHR, and that ACEI including DP exerts their antihypertensive effect through inhibition of vascular Ang II release in this animal model of human hypertension.