bluuebunny/crossref_metadata_2025 huggingface dataset:
CALCITONIN GENE RELATED PEPTIDE: VASODILATOR IN OVINE HEPATIC AND RENAL VASCULATURE
Authors: Fletcher David R. , Braslis Karl G. , Shulkes Arthur , Hardy Kenneth J.
Published: June 2007

1. Calcitonin gene‐related peptide (CGRP) is a product of alternate splicing of the calcitonin gene. It is found in nerves in the vasculature and is known from in vitro studies to be a potent vasodilator. It is found abnormally in the circulation of patients with medullary thyroid carcinoma (MTC) and has been proposed to be a cause of symptoms. This study was designed to determine the dose‐response effects of CGRP infusion in the intact conscious sheep on blood flow to liver and kidney, organs known to be richly innervated by CGRP‐containing nerves.

2. Blood flow was measured by an indicator dilution technique using [131I]‐labelled iodohippurate. CGRP infusion at both 1 and 5 pmol/kg per min produced significant (P<0.05) increases in both renal and hepatic blood flow. This increase in flow occurred despite a significant fall in perfusion pressure (P<0.05) at the higher infusion rate. At the highest infusion rate of 10 pmol/kg per min, when fall in perfusion pressure was even more marked, renal and hepatic blood flow was maintained.

3. We conclude that CGRP is vasodilatory in the renal and hepatic vascular beds and propose that nerves containing CGRP in those vessels may have a role in maintaining blood flow to those organs.
TIME COURSE OF RECOVERY OF β‐ AND α1‐ADRENOCEPTORS IN EXPERIMENTAL ASTHMA
Authors: Shindoh Joe , Sugiyama Satoru , Hayashi Kouichi , Takagi Kenzo , Satake Tatsuo , Ozawa Takayuki
Published: June 2007

1. The time course of recovery of reduced β‐adrenoceptors caused by ovalbumin (OA) challenge was investigated using guinea‐pigs.

2. The effects of prednisolone on the recovery time course were also evaluated.

3. β‐ and α1‐receptor assays were performed using lung membranes. Adenylate cyclase activity was also measured.

4. OA challenge reduced the number of β‐adrenoceptors by 35%, and a significant decrease (13%) persisted for 7 days. The number of β‐adrenoceptors recovered after 14 days.

5. OA challenge elevated the number of α1‐adrenoceptors. A significant increase (24%) was observed after 7 days, and it took a further 7 days for the recovery.

6. After OA challenge there was a significant decrease in adenylate cyclase activity after 7 days, which recovered after a further 7 days.

7. Inhalation of prednisolone accelerated the recovery of β‐adrenergic responsiveness, though it did not affect the recovery of the number of α1‐adrenoceptors. Prednisolone inhalation also elevated β‐adrenergic responsiveness in non‐asthmatic subjects.

8. It is concluded that reduced β‐adrenergic responsiveness caused by OA challenge persisted for 7 days and recovered after a further 7 days. Steroid hormone increased β‐adrenoceptors.
THE ANTINOCICEPTIVE ACTIONS OF KAVA COMPONENTS IN MICE
Authors: Jamieson D. D. , Duffield P. H.
Published: June 2007

1. The antinociceptive properties of the aqueous extract of the intoxicating beverage kava, and of the lipid soluble extract (kava resin) were tested in mice, by the tail immersion and abdominal constriction methods. Both extracts showed analgesic effects in both tests.

2. Eight purified pyrones from the lipid soluble extract were also tested for activity in the tail immersion test, and kawain, dihydrokawain, methysticin and dihydromethysticin were found to be very effective in producing analgesia. Using the tail immersion test the time course of action of the extracts of the four effective pyrones of kava were studied.

3. Naloxone, in doses which inhibited morphine‐induced analgesia in both tests, was completely ineffective in reversing the antinociceptive activities of the kava extracts, showing that analgesia produced by kava occurs via non‐opiate pathways.
POSITIVE INTERACTION OF ETHANOL AND KAVA RESIN IN MICE
Authors: Jamieson D. D. , Duffield P. H.
Published: June 2007

1. The lipid soluble extract of the psychoactive beverage kava has hypnosedative properties which can be measured by the length of time that the righting reflex is lost.

2. Ethanol and the lipid soluble extract (kava resin) have been shown greatly to increase each others hypnotic action in mice. Ethanol also increases the toxicity of kava markedly.

3. This interaction of kava and alcohol has important clinical and social consequences since, in contrast to traditional usage, kava is now often taken in conjunction with alcoholic drinks.
NORADRENALINE SENSITIVITY AND CALCIUM FLUXES IN ARTERIES FROM RABBITS WITH PERINEPHRITIS HYPERTENSION
Authors: Hall M. T. , Wadsworth R. M. , Kane K. A. , Hamilton C. A. , Reid J. L. , Rodger I. W.
Published: June 2007

1. Contractions of isolated vascular and cardiac preparations taken from rabbits with perinephritis (one kidney, one wrapped) hypertension were compared with those of preparations from control operated animals.

2. Significantly increased sensitivity to noradrenaline, which acts on α1‐adrenoceptors, was found in mesenteric arterial rings but not in aortic rings. The degree of hypersensitivity was the same in the presence and absence of cocaine, suggesting that there is no increase in uptake of noradrenaline into adrenergic nerves in this model of hypertension. In contrast to these agonist‐induced contractions, no increased sensitivity was found to potassium chloride, suggesting that hypersensitivity is specific for receptor mediated rather than membrane potential mediated effects.

3. No hypersensitivity to noradrenaline was found in the isolated left or right atria, which suggests that the hypertension is associated with changes in excitation–contraction coupling in blood vessels but not in cardiac muscle.

4. Hypertension increased basal 45Ca uptake in the mesenteric artery but not in the aorta. However, there was no significant difference between preparations from normotensive and hypertensive rabbits in 45Ca uptake or efflux stimulated by noradrenaline or KCl.

5. Increased basal 45Ca uptake could contribute to the increased sensitivity to noradrenaline found in the mesenteric artery in rabbit perinephritis hypertension.
CHANGES IN PREJUNCTIONAL POTENCY OF B‐HT 933 DURING AGING IN THE RAT VAS DEFERENS
Authors: Pagenkopf C. W. , Bourreau J‐P. , Challice C. E.
Published: June 2007

1. Age‐related changes in prejunctional α2‐adrenoceptors were examined in the rat vas deferens using pharmacological techniques.

2. B‐HT 933 (1 × 10‐8–1 × 10‐6 mol/L) caused a concentration‐dependent inhibition of isometric contractions (tetrodotoxin‐sensitive) induced by stimulation with single field‐stimulus pulses, in both the epididymal and prostatic regions of rat vas deferens. The concentration–response curve to B‐HT 933 was shifted to the right with age in the prostatic regions of the vas deferens.

3. In high concentrations (10‐6–3 × 10‐4 mol/L), B‐HT 933 caused concentration‐dependent enhancement of the contractile response to stimulation and evoked spontaneous contractile activity. No significant difference in this postjunctional activity occurred with age in either the prostatic or epididymal regions of the vas deferens.

4. Schild analysis revealed no significant differences in pA2 values for the antagonisms of the prejunctional inhibitory effect of B‐HT 933 by rauwolscine in either the prostatic or epididymal regions of vas deferens between young and old rats.

5. These results could be interpreted as a decrease in α2‐adrenoceptor number with age. The more marked decrease in the prejunctional inhibitory potency of B‐HT 933 in prostatic regions of vas deferens with aging may be due to a smaller receptor reserve in this region of the vas deferens.
SELECTIVE INHIBITION OF RESPONSES TO CARBACHOL AND McN‐A‐343 IN THE RABBIT VAS DEFERENS
Authors: Choo L. K. , Mitchelson F.
Published: June 2007

1. The effect of several selective muscarine receptor antagonists were evaluated on the responses of carbachol (CCh) and McN‐A‐343 (McN) during sympathetic nerve stimulation in the rabbit vas deferens.

2. The muscarine M1 receptor antagonist pirenzepine exhibited similar apparent pKB values for antagonism of the prejunctional inhibitory response of either CCh (pKB, 8.2) or McN (pKB, 8.5) on sympathetic nerve stimulation.

3. The muscarine M2 receptor antagonists, pancuronium and the bisalkyl ammonium compound ‘C7/3‐phth’ were selective inhibitors of the postjunctional facilitatory response produced by CCh on sympathetic nerve stimulation. They were also 17‐and three‐fold, respectively, less potent against the inhibitory responses of McN on sympathetic nerve stimulation. The apparent pKB value of pancuronium on the inhibitory response produced by CCh did not differ significantly (P>0.05) from that using McN. A similar finding was made for C7/3‐phth.

4. Selective blockade of the inhibitory response to CCh with pirenzepine (0.03 or 0.5 μmol/L) did not significantly (P>0.05) modify the apparent pKB value for pancuronium on the facilitatory response of CCh.

5. Selective blockade of the facilitatory response to CCh with a low concentration of pancuronium (0.5 μmol/L) did not significantly (P>0.05) modify the apparent pKB value for pancuronium (30 μmol/L) on the inhibitory response of CCh.

6. It is suggested that CCh and McN activate the same prejunctional M1 muscarine receptor and that pancuronium is the most selective of the muscarine M2 receptor antagonists presently tested in this preparation for distinguishing between muscarine M1 and M2 receptors.
GIRAFFES, RATS AND MAN – WHAT IS THE IMPORTANCE OF THE ‘STRUCTURAL FACTOR’ IN NORMO‐ AND HYPERTENSIVE STATES?
Authors: Folkow Björn
Published: June 2007

1. The normal structural adaptation of heart and vessels to regional changes in load or/and tissue demands is surveyed with respect to its importance for cardiovascular function in normotension as well as in physiological (giraffes) and pathophysiological (e.g. human and rat primary hypertension) variants of high pressure states.

2. At the local level it implies an entirely appropriate adjustment of cardiovascular geometric design according to principles inherent in the LaPlace and Poiseuille laws. However, when generalized to all systemic circuits, as in primary hypertension, it invites to a potentially dangerous positive feedback interaction with even ordinary functional pressor influences.

3. It is further emphasized how resistance vessels, besides the obvious influence of changes in: (i) vascular smooth muscle activity, are greatly affected also by changes of their (ii) geometric design, (iii) wall distensibility, and (iv) transmural pressure, how each of these four parameters can be independently altered and how they interact. Genetic reinforcements and various trophic influences may facilitate the extent and rate of ‘structural upward resetting’ in primary hypertension, and this resetting also encompasses the barostat mechanisms.

4. Against such a background it is, in fact, from a physiological point of view, more difficult to explain how 85–90% of the population manage to maintain lifelong normotension than to explain why hypertension gradually afflicts the remaining 10–15%. It points to the presence of potentially powerful and durable, negative feedbacks that are still poorly understood (e.g. Muirhead's renomedullary depressor system).

5. Considering the dominant haemodynamic influence of the structural factor in primary hypertension, it is finally stressed how the long‐range goal of antihypertensive treatment should be to cause full regression of the structural upward resetting, or perhaps even to prevent its early development in subjects predisposed for hypertension.
EVIDENCE FOR A ROLE FOR THE CARDIOVASCULAR AMPLIFIERS IN HUMAN PRIMARY HYPERTENSION
Authors: Jennings Garry , Korner Paul I. , Sudhir Krishnankutty , Esler Murray , Angus James A. , Laufer Eljas
Published: June 2007

1. Hypertrophy of vascular and cardiac smooth muscle is present in human primary hypertension. The amplifier properties associated with hypertrophy play a major role in maintaining hypertension.

2. Long‐term antihypertensive drug therapy causes substantial regression of the structural changes, assessed by the non‐autonomic component of vascular resistance, and by left ventricular mass. The latter occurs more slowly.

3. The more complete the reversal of left ventricular hypertrophy, the more slowly hypertension redevelops if long‐term antihypertensive therapy is discontinued.

4. Subjects who redevelop hypertension more rapidly tend to have higher cardiac output, suggesting that the cardiac amplifier may play a role in the pathogenesis.

5. Studies of small arteries and of veins from patients with primary hypertension suggest that there may be a general disturbance of vascular smooth muscle function, independent of the mechanical effects of elevated systemic blood pressure.
NEUROPEPTIDE Y AND CARDIOVASCULAR REGULATION
Authors: McCloskey D. I. , Potter Erica K.
Published: June 2007

1. The effects of neuropeptide Y (NPY) and related peptide fragments on blood pressure and vagal action at the heart were compared in the anaesthetized rat.

2. A change in vagal action was taken as a measure of presynaptic activity and a change in blood pressure was taken as a measure of postsynaptic activity.

3. NPY, NPY‐(13‐36) and a stabilized 13‐36 analogue of NPY (ANA NPY) all exerted pressor actions and attenuated vagal action at the heart.

4. On the basis of different potencies demonstrated for the pressor and vagal inhibitory actions of these peptides, the results are consistent with the proposal that there are two populations of NPY receptors.
CARDIOVASCULAR FUNCTIONS OF CENTRAL NORADRENERGIC NEURONS IN RABBITS
Authors: Head Geoffrey A.
Published: June 2007

1. The cardiovascular actions of central noradrenergic (NA) neurons was examined using the acute neurotransmitter releasing actions of intracisternal 6‐hydroxydopamine in conscious rabbits.

2. The predominant actions of NA pathways in the brain‐stem are to inhibit vasomotor and cardiac sympathetic activity and to facilitate cardiac vagal responses.

3. NA projections to the spinal cord tonically inhibit vasoconstrictor tone and form part of a high gain control system for responding to changes in specific afferent information.

4. The forebrain NA projections influence heart rate through modulation of the baroreflex gain of the cardiac vagus.

5. Central antihypertensive drugs such as clonidine and α‐methyldopa mimic most of the brain‐stem actions of the central NA neurons. They also utilize the ascending NA pathways influencing the baroreflex vagal gain to minimize the baroreflex effects of reducing mean arterial pressure.

6. Thus, NA neurons influence the circulatory system through actions at all levels of the central nervous system and provide a comprehensive framework for integrating cardiovascular information from multiple inputs. This provides a number of targets for future development of useful pharmacological agents.
THE USE OF NON‐INVASIVE BLOOD PRESSURE MEASUREMENTS TO MEASURE PRESSOR RESPONSES IN RATS DURING AIR STRESS
Authors: Spanos H. G. , DiNicolantonio R. , Morgan T. O.
Published: June 2007

1. A non‐invasive tail cuff method was validated against direct intra‐arterial blood pressure measurements (r2 >0.9) and then used to measure the systolic blood pressure (SBP) responses to air‐jet stimulation in mature conscious Sprague‐Dawley (SD) and spontaneously hypertensive rats (SHR). The experiments with the SHR were conducted in parallel with age matched SD rats.

2. All rats were trained to remain in perspex holders and when their SBP had stabilized, a jet of air of 10 min duration was directed at the rat's nose via rubber tubing. The blood pressure was measured during the first, fifth and tenth minute.

3. The maximum SBP response normally occurred during the first min of air‐jet stimulation and averaged + 30 mmHg in the SHR and +21 mmHg in the SD. Although of higher magnitude in the SHR, when expressed as a percentage of the control SBP, the rise was similar for both strains, 13% and 14%, respectively.

4. The pressor response of three SD rats stimulated daily for up to 12 days did not show any evidence of habituation to the stimulus.

5. The pressor responses to air‐jet stimulation were abolished in anaesthetized rats, suggesting that they are primarily higher centre responses.
NORMOTENSIVE WISTAR RATS DIFFER FROM SPONTANEOUSLY HYPERTENSIVE AND RENAL HYPERTENSIVE RATS IN THEIR CARDIOVASCULAR RESPONSES TO OPIOID AGONISTS
Authors: Tyszkiewicz Ewa Widy‐ , Czlonkowski Andrzej
Published: June 2007

1. The effects of three opioid receptor agonists on the blood pressure and heart rate of anaesthetized normotensive, spontaneously hypertensive and renal hypertensive rats were measured.

2. Mu agonist morphiceptin i.c.v. induced a pressor response and increase in heart rate in hypertensive rats, but hypotension in normotensive rats. After intravenous (i.v.) injection, morphiceptin produced a hypotensive response in all three groups of rats.

3. In contrast, the delta agonist DTLET i.c.v. decreased blood pressure and heart rate in hypertensive rats, but increased both pressure and beat rate in normotensive rats. After i.v. injections DTLET produced a hypertensive response and increase in heart rate in all groups of rats.

4. Kappa agonist U‐50, 488H given i.c.v. induced effects similar to morphiceptin: an increase in blood pressure and heart rate in hypertensive and a decrease in normotensive rats. After i.v. injections U‐50, 488H produced decreases in blood pressure and heart rate in all treated groups of rats.

5. Pretreatment with naloxone antagonized the activity of morphiceptin but prevented only the stimulating effect of DTLET in normotensive rats. Cardiovascular actions of U‐50, 488H were not blocked by naloxone.

6. The results suggest that opioid agonists exert similar changes in cardiovascular function at central and peripheral sites in both models of experimental hypertension and these effects are different in normotensive rats.
RENAL SODIUM EXCRETION FOLLOWING SYSTEMIC INFUSION OF VASOACTIVE INTESTINAL PEPTIDE IN THE RAT
Authors: Lonergan M. A. , Field M. J.
Published: June 2007

1. The aim of this clearance study was to examine the renal effects of systemic infusion of vasoactive intestinal peptide (VIP) in the intact rat.

2. Mean arterial blood pressure (MAP), plasma electrolytes and haematocrit, glomerular filtration rate (GFR), and urinary sodium and potassium excretion were measured in a baseline period and following VIP infusion (0.1–1.2 nmol/h per 200 g), as well as during a time control study.

3. During infusion of low doses of VIP (0.1 and 0.4 nmol/h per 200 g), a small increase in fractional and absolute excretion of sodium occurred but this did not differ from that occurring in the time control group. In the high dose VIP group (1.2 nmol/h per 200 g), significant falls occurred in MAP and GFR, and absolute sodium excretion fell (though not significantly) from its baseline level.

4. These findings suggest that systemic VIP has no net natriuretic effect in the rat, but produces haemodynamic changes associated with reduced sodium excretion at high doses. This study does not exclude the possibility of direct effects on tubular sodium transport of VIP released from renal nerves.
EFFECTS OF OPIATES ON SODIUM EXCRETION IN THE ISOLATED PERFUSED RAT KIDNEY
Authors: Ellis Andrew G. , Adam William R.
Published: June 2007

1. A rat isolated perfused kidney preparation was utilized to define clearly a renal site of action. The variables measured were perfusate pressure and flow, glomerular filtration rate, urine volume, sodium excretion and potassium excretion.

2. Dextromethorphan (3 nmol/L) and dextrorphan (10 nmol/L) reduced sodium excretion in kidneys from rats on either control or high K+ diet, in the absence of any other measured renal effects. Dextromethorphan (10 nmol/L) produced a decrease in glomerular filtration rate as well as a decrease in sodium excretion. Naloxone (1 μmol/L) inhibited the effect of dextromethorphan on sodium excretion but had no effect when administered alone.

3. The levorotatory opiates levorphanol and levomethorphan, the kappa agonist ketocyclazocine and a range of other opiates had no effect on sodium excretion.

4. The results suggest a renal action specific for dextrorotatory opiates. This renal action is consistent with earlier binding studies suggesting preferential recognition of dextrorotatory opiates.
FUTURE DIRECTIONS FOR RESEARCH INTO DIETARY AND OTHER LIFESTYLE FACTORS IN HYPERTENSION
Authors: Beilin L. J.
Published: June 2007

1. Directions for future research into dietary and other lifestyle factors which influence blood pressure can only be signposted at this stage. It is suggested that eight parallel and interrelated paths merit attention.

2. The following questions might be addressed. Which techniques measure lower blood pressure most effectively? How do different environmental factors interact with one another and what is their influence on physiological control mechanisms? How do genetic and environmental influences interrelate? How can behavioural change be more readily achieved? What role if any do stress and personality play in hypertension? What are the relative costs and benefits of drug and non‐drug measures in the management of hypertension? Finally what are the most effective ways of reducing the cardiovascular morbidity and mortality associated with hypertension?
POLYAMIDE‐OLIGONUCLEOTIDE HYBRID MOLECULES
Authors: Haralambidis Jim , Coghlan John P.
Published: June 2007

1. Recent experience with polyamide–oligonucleotide hybrids shows the versility of this approach for replacement of radioactive isotopes for detection of hybridization on gels and for hybridization histochemistry.

2. These molecular hybrids also show great promise as antisense inhibitors.
CARDIAC CHEMORECEPTORS: PHARMACOLOGICAL CURIOSITIES OR PHYSIOLOGICAL TOOLS?
Authors: Ludbrook John , Evans Roger G.
Published: June 2007

1. We have tested in unanaesthetized rabbits two hypotheses regarding a physiological role for cardiogenic chemoreflexes in acute central hypovolaemia.

2. In rabbits, the sympathoinhibitory phase of acute central hypovolaemia depends on the activation of a brain‐stem δ‐opioid receptor mechanism by a signal from the heart. Blockade of this by fourth ventricular injection of the δ‐receptor antagonist ICI 174864 had no effect on the reflex haemodynamic responses to left atrial phenylbiguanide or intrapericardial nicotine.

3. Intravenous administration of the 5‐HT3 receptor antagonist MDL 72222, or intrapericardial administration of the nicotinic ganglionic cholinoceptor antagonist mecamylamine HCl, had no effect on the haemodynamic response to acute central hypovolaemia.

4. We conclude that phenylbiguanide‐sensitive myocardial afferents and nicotine‐sensitive epicardial afferents play no part in the response to acute hypovolaemia in rabbits, and that the reflex effects evoked by chemically exciting these afferents do not depend on a brain‐stem δ‐opioid mechanism.
THERE ARE FEW CATECHOLAMINE‐ OR NEUROPEPTIDE Y‐CONTAINING SYNAPSES IN THE INTERMEDIOLATERAL CELL COLUMN OF RAT THORACIC SPINAL CORD
Authors: Llewellyn‐Smith Ida J. , Minson Jane B. , Pilowsky Paul M. , Chalmers John P.
Published: June 2007

1. A quantitative electron microscopic immunocytochemical technique was used to assess the number of synapses immunoreactive for tyrosine hydroxylase (TH), phenylethanolamine N‐methyltransferase (PNMT) and neuropeptide Y (NPY) in the intermediolateral cell column in segments T2 and T3 of rat thoracic spinal cord.

2. TH synapses comprised about 5%; PNMT synapses 1–2%; and NPY synapses 1–2% of the total number of synapses in the intermediolateral cell column. All three types of synapses were predominantly or exclusively on dendrites.

3. Our results suggest that catecholamine/NPY neurons may not provide a major synaptic input to sympathetic preganglionic neurons in rat upper thoracic spinal cord.
ENHANCED MYOCARDIAL METABOLISM IMPROVES RECOVERY AFTER CARDIAC SURGERY AND TRANSPLANTATION
Authors: Rosenfeldt F. L. , Munsch C. , Langley L. , Conyers R. , Williams J. F.
Published: June 2007

Over the past 15 years many of the advances in the science of cardiac surgery have involved methods of protecting the heart against damage during operations. Hypothermic cardioplegia has become the preferred technique of protection. This involves supporting the circulation using the heart‐lung machine, arresting the heart with a potassium‐containing solution and maintaining a low myocardial temperature to minimize energy needs. This technique relies mainly on anaerobic metabolism to maintain cardiac viability.
THE ROLE OF THE MACULA DENSA IN RENIN SYNTHESIS
Authors: Morgan Trefor , Barrett Graham , Zhang Yanling , Alcorn Daine
Published: June 2007

1. The role of the macula densa in renin synthesis was studied using mice with one hydronephrotic kidney.

2. Renin synthesis was assessed by measurement of renal renin, renal mRNA for renin and plasma renin.

3. Sodium depletion stimulated mRNA and renal renin to a similar extent in the hydronephrotic and contralateral kidney.

4. Enalapril stimulated mRNA concentration in both kidneys but renal renin did not rise in the hydronephrotic kidney.

5. Propranolol did not alter the response to sodium depletion in either kidney.

6. The macula densa is not crucial for the stimulation of renin synthesis following sodium depletion. However, it may regulate renin production after mRNA synthesis, possibly by controlling the conversion of prorenin to renin.
ENDOTHELIN‐1 ENHANCES VASOCONSTRICTOR RESPONSES TO SYMPATHETIC NERVE STIMULATION AND NORADRENALINE IN THE RABBIT EAR ARTERY
Authors: Wong‐Dusting Helen K. , La Mylinh , Rand Michael J.
Published: June 2007

1. In rabbit isolated perfused ear arteries denuded of endothelium, a low concentration of endothelin‐1 (0.1 nmol/L) that had no direct vasoconstrictor action produced slowly developing enhancements of vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation. The enhancements reached maximal levels after 60 min of exposure to endothelin‐1.

2. A higher concentration of endothelin‐1 (1 nmol/L), which produced a slow‐developing increase in perfusion pressure of 70 mmHg over the course of 1 h, significantly enhanced vasoconstrictor responses to sympathetic nerve stimulation for the first 30 min, after which there was no significant enhancement. Responses to noradrenaline were not enhanced by 1 nmol/L endothelin‐1.

3. The enhancing effect of low concentrations of endothelin‐1 on vasoconstrictor responses to sympathetic nerve stimulation and noradrenaline may play a physiological role in modulating vasomotor function.
ORTHOSTATIC AND POSTPRANDIAL BLOOD PRESSURE REDUCTION IN PATIENTS WITH ESSENTIAL HYPERTENSION
Authors: Masuo Kazuko , Mikami Hiroshi , Habara Nanao , Ogihara Toshio
Published: June 2007

1. The role of the sympathetic nervous system in orthostatic and postprandial blood pressure reduction in patients with essential hypertension was studied in 13 hypertensive patients and 10 age‐matched normotensive subjects.

2. The blood pressure (BP), pulse rate, and plasma norepinephrine (NE) were measured: (i) every minute for 20 min in the upright position after overnight recumbency (ii) every 30 min after food intake for 3 h in the supine position.

3. Orthostatic BP reduction (> 13 mmHg in mean BP) was observed in eight hypertensive patients with a maximum after 4 min. Seven of these patients showed postprandial hypotension (> 13 mmHg) with a maximum 90 min after eating, while none of the normotensives exhibited such BP reductions. Before and during the tests the plasma NE levels were higher in hypertensive patients than in the normotensives. The plasma NE level was increased from 370±80 to 790±110 pg/mL 4 min after standing (P<0.01) in hypertensive patients and from 220±40 to 530±90 pg/mL (P<0.01) in normotensive subjects. The plasma NE level was decreased 90 min after food intake from 390±90 to 260±80 pg/mL in hypertensives. Changes in plasma NE correlated with those in mean BP after standing for 4 min (r= 0.379, P<0.05) and also with those 90 min after food intake (r= 0.457, P<0.05).

4. These findings suggest that patients with essential hypertension have abnormally increased basal sympathetic nerve activity at rest, and that their orthostatic and postprandial BP reductions may both be caused by impairment of the sympathetic nervous system and of cardiovascular reflexes.
MECHANISMS OF LIDOCAINE ACTIONS ON NORMAL AND ABNORMAL RHYTHMS IN CANINE CARDIAC TISSUES IN VIVO AND IN VITRO
Authors: Abete P. , Ferrara N. , Rengo F. , Vassalle M.
Published: June 2007

1. The actions of lidocaine on cardiac pacemaker rhythms were studied in anaesthetized dogs and in Purkinje fibres from hearts of the same animals.

2. In vivo, lidocaine (1 mg/ kg, intravenously) slowed the sino‐atrial (SA) node rhythm (– 5.0%), and (during vagal stimulation) prolonged ventricular standstill by + 25.1% and slowed the idioventricular rhythm (– 16.7%). A higher dose (4 mg/kg) had more pronounced effects.

3. Propranolol also slowed sinus (– 26.2%) and idioventricular (– 27.2%) rhythms, and prolonged ventricular standstill (+ 36.8%). In the presence of propranolol, the effects of lidocaine on idioventricular rhythm were exaggerated.

4. In Purkinje fibres driven in vitro, lidocaine (10 μmol/L) decreased contractile force (– 47.9%) and (during the interruption of drive) prolonged the suppression of (+ 53.2%) and slowed the escape rhythm (– 67.0%).

5. In the presence of lidocaine the threshold potential was shifted to less negative values and diastolic depolarization slope was decreased (– 23.6%).

6. Lidocaine slowed spontaneously active Purkinje fibres, abolished early afterdepolarizations in low [K]0 and slow responses in high [K]0 (by shifting the threshold to less negative values), and antagonized strophanthidin arrhythmias.

7. TTX reduced the hyperpolarization by lidocaine in low [K]0 and vice versa.

8. We conclude that lidocaine enhances vagally‐induced ventricular standstill by depressing the idioventricular rhythm far more than the sinus rhythm, an action enhanced by beta‐blockade. Furthermore, lidocaine depresses normal and different types of abnormal automaticity through direct and indirect effects of the blockade of the fast sodium channel.
ROLE OF THE SYMPATHETIC NERVOUS SYSTEM IN THE ONSET OF HYPERTENSION IN THE RAT: THE EFFECT OF 6‐OH‐DOPAMINE
Authors: Li Ming , Whitworth Judith A.
Published: June 2007

1. The effect of chemical sympathectomy with 6‐OH‐dopamine (6‐OHDA) on the onset of adrenocorticotrophin (ACTH)‐induced hypertension was examined in Sprague–Dawley rats (n= 23).

2. 6‐OHDA injection produced a fall in systolic blood pressure (SBP) from 100±5 mmHg control to 74±4 mmHg post‐6‐OHDA Treatment Day 1 (P<0.001), but did not alter food or water intake, urine volume or electrolyte excretion.

3. Compared with sham injection, ACTH‐treated rats showed an increase in blood pressure (sham: 98±7 mmHg; ACTH: 123±9 mmHg on Treatment Day 10; P<0.01), loss of bodyweight, and increases in water intake and urine volume.

4. The magnitude of the blood pressure rise on ACTH was greater in 6‐OHDA‐treated rats than in intact control rats. Metabolic changes were similar.

5. Chemical sympathectomy with 6‐OHDA did not delay or block the onset of ACTH hypertension in the rat.
REPERFUSION ARRHYTHMIAS IN CLOSED‐CHEST RATS: THE EFFECT OF MYOCARDIAL NORADRENALINE DEPLETION AND Ca2+‐ANTAGONISM
Authors: Kirchengast Michael , Hergenröder Stefan
Published: June 2007

1. The influence of myocardial noradrenaline depletion on the incidence and severity of reperfusion arrhythmias in closed‐chest anaesthetized rats was investigated. Five‐minute left coronary artery occlusion was carried out via an implanted occluder. Four groups of rats were studied: controls, rats treated with reserpine (5 mg/kg, intraperitoneally) 24 h before occlusion, and rats receiving 0.2 mg/kg gallopamil intravenously 5 min before occlusion either with or without reserpine pretreatment.

2. In the control group all animals had ventricular tachycardia (VT) and fibrillation (VF) immediately after reperfusion. Gallopamil reduced VT to 50% and VF to 25% (P<0.05 versus control). In the reserpine group all had VT, and 67% had VF, this being not significantly different from controls. Additional treatment with gallopamil markedly reduced VT and totally prevented VF (P<0.05 versus control).

3. Thus, total depletion of myocardial noradrenaline stores neither prevented the occurrence nor reduced the severity of reperfusion arrhythmia in rats, while gallopamil treatment was effective.
INVESTIGATIONS INTO INTERACTIONS BETWEEN DOXAZOSIN AND ENALAPRILAT AT α1‐ADRENOCEPTORS IN ANAESTHETIZED RATS
Authors: Marwood John , Tierney Garth , Stokes Gordon
Published: June 2007

1. In anaesthetized intact Sprague‐Dawley rats, the angiotensin‐converting enzyme inhibitor enalaprilat, 1 mg/kg, had no significant effect on the pressor responses to the α1‐adrenoceptor agonist phenylephrine (PE). Doxazosin 1 mg/kg was found to be a potent α1‐adrenoceptor antagonist.

2. The combination of enalaprilat 1 mg/kg plus doxazosin 1 mg/kg was 3.3‐fold more potent in antagonizing α1‐adrenoceptors than doxazosin 1 mg/kg alone.

3. After treatment of rats with deoxycorticosterone acetate (DOCA) twice weekly for 5 weeks, the α1‐adrenoceptor antagonist action of doxazosin in anaesthetized rats was not potentiated by enalaprilat 1 mg/kg.

4. Since DOCA treatment suppresses renin activity, these findings strongly support the hypothesis that angiotensin II can modulate the functional activity of α1‐adrenoceptor in vascular smooth muscle.
EFFECTS OF DIETARY SODIUM RESTRICTION AND FISH OIL SUPPLEMENTS ON BLOOD PRESSURE IN THE ELDERLY
Authors: Cobiac Lynne , Nestel Paul J. , Wing Lindon M. H. , Howe Peter R. C.
Published: June 2007

1. The effects on blood pressure of dietary fish oil, sodium restriction and a combination of both strategies were examined in a short‐term dietary intervention study of 50 healthy elderly subjects (average age 67 years) with mean initial systolic and diastolic blood pressures of 133 and 77 mmHg, respectively.

2. Subjects were allocated to one of four treatment groups: fish oil with normal sodium, fish oil with low sodium, sunflower oil with normal sodium and sunflower oil with low sodium for 4 weeks. They then crossed over to the alternative sodium treatment for a further 4 weeks whilst remaining on the same oil.

3. The combination of fish oil supplementation with dietary sodium restriction caused significant reductions of blood pressure in the first 4 weeks: systolic blood pressure (SBP) fell by 8.9 mmHg, mean arterial pressure (MAP) by 7.4 mmHg and diastolic blood pressure (DBP) by 6.0 mmHg.

4. Fish oil enhanced the effect of sodium restriction on blood pressure. In the crossover protocol, a change in sodium excretion of 92 mmol/day was accompanied by changes of 6.4, 3.3 and 2.2 mmHg for SBP, MAP and DBP, respectively, in the subjects taking fish oil. However in those taking sunflower oil, blood pressure did not change significantly.

5. The results indicate beneficial interactive effect of dietary fish oil and sodium intake on blood pressure.
POTASSIUM, GLUCOSE, INSULIN INTERRELATIONSHIPS DURING ADRENALINE INFUSION IN NORMOTENSIVE AND HYPERTENSIVE HUMANS
Authors: Gordon Richard D. , Bachmann Anthony W. , Ballantine Donna M. , Thompson Robyn E.
Published: June 2007

1. Significant increases in arterial noradrenaline (NA) of similar magnitude were seen in normotensive (NT) and hypertensive humans (HT) during adrenaline (ADR) infusion.

2. Significant falls in plasma potassium (K+) were observed in both NT and HT during ADR infusion, even at rates equivalent to minor stress. Levels achieved were significantly lower in HT than in NT.

3. Plasma glucose increased significantly in HT at all ADR infusion rates but only at higher rates of infusion in NT.

4. Basal insulin levels were significantly higher in NT than in HT. After cessation of infusion, insulin increased three‐fold in HT and two‐fold in NT.

5. Infusion of ADR to produce levels seen during mild to moderate stress resulted in significant increases in plasma NA, falls in plasma K+ and increases in plasma glucose. The expected large insulin response to rising glucose was not seen until after ADR was ceased, confirming the inhibitory effect of ADR on glucose stimulated insulin release.
DOES URINARY ATRIAL NATRIURETIC PEPTIDE REFLECT PLASMA LEVELS IN HUMANS?
Authors: Tunny Terry J. , Finn Wendy L. , Klemm Shelley A. , Gordon Richard D.
Published: June 2007

1. Saline infusion produced concurrent mean increases over basal in plasma and urinary atrial natriuretic peptide (ANP) of approximately 100%.

2. Subpressor calcium infusion also produced concurrent increases in plasma and urinary ANP of 38 and 60% respectively.

3. Urinary ANP appeared to be as responsive to the dynamic stimulation of saline and calcium infusion as plasma levels.

4. Urinary ANP may be useful when an integrated estimation of ANP secretion and metabolism is required. Further studies are required to assess clinical utility in a variety of settings, for example during endopeptidase 3.4.24.11 inhibition.
HAEMODYNAMIC AND HORMONAL EFFECTS OF N‐NITRO‐l‐ARGININE, AN INHIBITOR OF NITRIC OXIDE BIOSYNTHESIS, IN SHEEP
Authors: Tresham J. J. , Dusting G. J. , Coghlan J. P. , Whitworth J. A.
Published: June 2007

1. The haemodynamic and hormonal responses to N‐nitro‐l‐arginine (NOLA), a potent inhibitor of nitric oxide biosynthesis in endothelial cells, were investigated in conscious sheep.

2. Mean arterial blood pressure (MAP), heart rate (HR) and cardiac output by thermodilution (CO) were measured in four oophrectomized ewes. Two other ewes were surgically implanted with aortic electromagnetic flow probes and an indwelling carotid arterial line for monitoring CO and MAP over 40 h.

3. After a control period, NOLA (10 mg/kg) was injected intravenously and MAP, HR and CO monitored and blood samples taken at intervals over the following 24 h.

4. NOLA increased blood pressure within minutes, from 76 ± 4 to a maximum of 99 ± 4 mmHg (P<0.001) at 6 h after injection. It remained elevated 24 h after injection. CO and HR fell but these falls were not sustained longer than 6 h. Calculated total peripheral resistance increased to a maximum of 2 h, but had returned to control levels 24 h after injection. There were no significant changes in plasma concentrations of renin, atrial natriuretic factor, vasopressin, noradrenaline or endothelin during the first hour.

5. NOLA may be a useful tool in understanding the role of the endothelium and nitric oxide in the control of blood pressure.
EFFECTS OF V2 RECEPTOR ACTIVITY ON THE PRESSOR RESPONSE TO VASOPRESSIN IN THE RAT
Authors: Shimizu Keishi , Schwartz Jeffrey , McGrath Barry P.
Published: June 2007

1. To determine the contribution of V1 and V2 receptor activity on the enhancement of reflex buffering of the pressor response to arginine‐vasopressin (AVP), mean arterial pressure (MAP) and heart rate (HR) changes were examined in response to graded injections of phenylephrine, AVP, or Phe2Orn8OT, a potent, selective V1‐receptor agonist in the absence and presence of Val4DArg8VP, a potent, selective V2‐receptor agonist.

2. There were no significant differences in MAP responses to the V1 agonist in the absence and presence of the V2 agonist in either conscious intact or autonomic‐blocked rats.

3. Autonomic blockade with methscopolamine and hexamethonium increased the pressor sensitivity to phenylephrine threefold. In contrast, the pressor sensitivities to AVP and Phe2Orn8OT were increased 14‐fold and 11‐fold, respectively, by autonomic blockade.

4. V2‐receptor activity does not have any inherent vasocative action or synergistic vasoactive action with V1‐receptor activity.

5. V2 receptors do not play a role in enhancing reflex buffering of the pressor response to AVP; V1 receptors are suggested to play the role.
PRESYNAPTIC REGULATION OF NEUROTRANSMITTER RELEASE IN HYPERTENSION
Authors: Tsuda Kazushi , Masuyama Yoshiaki
Published: June 2007

1. The present review discusses evidence in support of the concept that alterations in sympathetic neurotransmitter release might contribute to the pathogenesis of hypertension.

2. Studies suggest that changes in sympathetic nervous activity in both the central and peripheral nervous systems participate in blood pressure control.

3. In the periphery increased release of norepinephrine from vascular adrenergic neurons might lead to the enhanced vasoconstrictor responses and thus to an elevation in systemic blood pressure.

4. The amount of neurotransmitter release from sympathetic nerve endings can be regulated by autoregulatory systems by presynaptic receptors located on nerve terminals.

5. It has been proposed that alterations to sympathetic nervous activity of hypertension might be partially due to abnormalities in presynaptic modulation of neurotransmitter release in central and peripheral tissues.

6. This article summarizes the results of studies to evaluate presynaptic receptor functions and sympathetic neurotransmitter release in hypertension.
EVIDENCE AGAINST THE INVOLVEMENT OF VASOACTIVE INTESTINAL PEPTIDE IN OVINE PAROTID SECRETION AND BLOOD FLOW
Authors: Wright R. D. , Blair‐West J. R. , Gibson A. P. , Shulkes A.
Published: June 2007

1. The proposition that stimulation of the secretomotor nerve to the ovine parotid gland might involve co‐release of vasoactive intestinal peptide (VIP) was tested by studying responses to infusion of VIP directly into the gland's arterial blood supply and by assay of VIP in parotid venous blood.

2. In unstimulated glands, an arterial blood concentration of 1.5–2.5 X 10−9 mol/L VIP did not evoke fluid secretion but it increased K+ and phosphate secretion and glandular blood flow. The same blood concentration of VIP potentiated the stimulation of salivary flow rate caused by intraarterial infusion of bethanechol but nerve stimulation was not potentiated. VIP increased glandular blood flow in both conditions of stimulation.

3. Atropine blocked neurally stimulated salivary secretion but an increase in glandular blood flow was still detectable. There was therefore no evidence for a non‐cholinergic neural mechanism for salivary secretion.

4. Furthermore, VIP concentrations in glandular venous blood were not increased by nerve stimulation.

5. The results indicate that exogenous VIP can affect the flow and composition of ovine parotid secretion but was not involved in the response to secretomotor nerve stimulation.
DIRECT AND INDIRECT STIMULATION OF PANCREATIC EXOCRINE SECRETION BY NEUROTENSIN IN ANAESTHETIZED DOGS
Authors: Iwatsuki K. , Horiuchi A. , Ren L‐M. , Chiba S.
Published: June 2007

1. The effects of neurotensin on pancreatic exocrine secretion were investigated both in the intact whole pancreas and in the isolated, blood‐perfused pancreas ex vivo in anaesthetized dogs.

2. Intravenous (i.v.) injections of neurotensin (0.01‐1 nmol/kg) elicited dose‐dependent increases in the secretory rate of pancreatic juice without changes in plasma levels of cholecystokinin (CCK). The concentration of bicarbonate in the pancreatic juice induced by neurotensin was increased, but the protein concentration was scarcely changed.

3. The neurotensin‐induced secretion was inhibited by SCH23390, a dopamine D‐1 antagonist, but not by domperidone, phentolamine, propranolol, atropine, cimetidine, or L‐364,718, a CCK antagonist.

4. Intra‐arterial (i.a.) injections of neurotensin (0.1‐3 nmol/kg) also elicited dose‐dependent increases in the secretory rate of pancreatic juice flow, but did not change bicarbonate or protein concentration. The secretory activities were less effective and 1 nmol/kg of neurotensin i.a. was approximately equal to that of 0.03 nmol/kg of neurotensin i.v.

5. These results suggest that neurotensin mainly stimulates pancreatic secretion by acting indirectly. Neurotensin‐induced secretion is, at least in part, mediated by endogenously released dopamine which activates dopamine D‐1 receptors on the pancreas. In addition to its indirect action, neurotensin has a weak direct action to stimulate pancreatic secretion.
IN VITRO AUTORADIOGRAPHIC ENDOTHELIN‐1 BINDING SITES AND SARAFOTOXIN S6B BINDING SITES IN RAT TISSUES
Authors: Kohzuki Masahiro , Johnston Colin I. , Abe Keishi , Chai Siew Yeen , Casley David J. , Yasujima Minoru , Yoshinaga Kaoru , Mendelsohn Frederick A. O.
Published: June 2007

1. The distribution of binding sites for [125I]‐labelled endothelin‐1 ([125I]‐ET‐1) and [125I]‐labelled sarafotoxin S6B ([125I]‐SRT) was visualized in rat tissues using in vitro autoradiography.

2. A high density of endothelin‐1 (ET‐1) binding was found in the heart. In the kidney, ET‐1 binding occurred in association with glomeruli, proximal tubules, the inner stripe and inner medulla. In the adrenal, a high density of ET‐1 binding occurred in the medulla as well as the zona glomerulosa.

3. The binding affinity constant (KA) for ET‐1 binding in these sites ranged from 1 to 10 X 109/mol per litre.

4. Although sarafotoxin S6B (SRT) was 10–100‐fold weaker than ET‐1 in displacing [125I]‐ET‐1 from these sites, 1 μmol/L unlabelled SRT completely abolished [125I]‐ET‐1 binding in all sites. Other venom peptides did not affect [125I]‐ET‐1 binding.

5. The pattern of [125I]‐SRT receptor binding in rat tissues by in vitro autoradiography was identical to that for ET‐1 receptor binding, and both unlabelled SRT and unlabelled ET‐1 fully competed with [125I]‐SRT for binding.

6. These results provide evidence that SRT binds to the ET receptor in a range of rat tissues. The results suggest that there may be subclasses of ET receptors which can be distinguished by the relative potencies of ET‐1 and SRT at various tissues.
ATRIAL NATRIURETIC PEPTIDE INHIBITS THE ALDOSTERONE RESPONSE TO METOCLOPRAMIDE IN PATIENTS WITH GLOMERULAR DISEASE AND ESSENTIAL HYPERTENSION
Authors: Matsuoka Hiroaki , Fukui Kazushige , Dan Yoshiyuki , Ishimitsu Toshihiko , Hirata Yasunobu , Kimura Kenjiro , Sugimoto Tsuneaki , Ishii Masao , Kangawa Kenji , Matsuo Hisayuki
Published: June 2007

1. We examined the effects of metoclopramide (MCP: 10 mg i.v.) on plasma atrial natriuretic peptide (ANP) and aldosterone concentrations (PAC) and the effect of ANP on MCP‐induced PAC in four patients with primary glomerular diseases and seven patients with essential hypertension.

2. MCP injection caused no significant changes in plasma ANP. MCP produced a marked increase in PAC without a significant change in plasma renin activity.

3. The increase in PAC induced by MCP injection was markedly attenuated when preceded by the infusion of ANP (25 ng/kg per min).

4. These results suggest that the dopaminergic D2 mechanism is not involved in the regulation of ANP secretion and that ANP modulates the dopaminergic regulation of aldosterone secretion.