bluuebunny/crossref_metadata_2025_split huggingface dataset:
INTERACTION BETWEEN EPIDERMAL GROWTH FACTOR AND ARGININE VASOPRESSIN IN RENAL MEDULLARY MEMBRANES
Authors: Grant S. L. , Phillips P. A. , Gow C. B. 
Published: June 2007

SUMMARY1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin‐induced water reabsorption.2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes.3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither.4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (CAMP) production was inhibited by epidermal growth factor (IC50 2 ± 10−7 mol/L) as was sodium fluoride cAMP production but only at much higher concentrations.5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system.
PROCEEDINGS OF THE HBPRCA DIFFERENTIAL EFFECT OF RENAL WRAP HYPERTEN SION ON AORTIC SMOOTH MUSCLE POLYPLOIDY IN THE RAT AND RABBIT
Authors: Black M. Jane , Campbell Julie H. , Campbell Gordon R. 
Published: June 2007

SUMMARY1. The incidence of aortic smooth muscle cell polyploidy was investigated in rabbits and rats with renal wrap induced (cellophane perinephritic) chronic hypertension.2. Bilateral renal cellophane wrapping was performed in young adult animals. Blood pressure was measured intra‐arterially in the rabbits twice during the experimental period and tail‐cuff blood pressure measured twice weekly in the rats. At 8 weeks post‐surgery the incidence of aortic smooth muscle cell polyploidy was determined in enzymatically isolated cells by flow cytometric DNA analysis.3. Systolic blood pressure was significantly increased in the bilateral renal wrapped rabbits and rats compared to the shams, such that at 8 weeks post‐surgery, systolic blood pressure was 139 ± 2 mmHg and 84±2 mmHg, respectively, in the rabbits and 188±6 mmHg and 155±4 mmHg, respectively, in the rats.4. The incidence of polyploid smooth muscle cells was significantly higher in the hypertensive renal wrapped rat compared to the sham (20.9±1.5% and 8.1±0.5%, respectively). However, the incidence of polyploid cells was low in the rabbit aortae with no significant difference in the incidence of aortic smooth muscle polyploidy in the hypertensive rabbit compared to the sham (2.6 ± 0.6% and 2.7 ± 0.6%, respectively).5. This study demonstrates a species difference in the induction of polyploidy during the same model of experimental hypertension in aortic smooth muscle derived from the rabbit and rat.
MITOGENIC ACTIONS OF ENDOTHELIN‐1 AND EPIDERMAL GROWTH FACTOR IN CULTURED AIRWAY SMOOTH MUSCLE
Authors: Stewart Alastair G. , Grigoriadis George , Harris Trudi 
Published: June 2007

SUMMARY1. Hyperplasia of airway smooth muscle contributes to the increase in bronchomotor responsiveness that characterizes asthma. We have investigated the mitogenic potential of endothelin‐1 (ET‐1) and epidermal growth factor (EGF) in guinea‐pig cultured airway smooth muscle and the relationship of these actions to tyrosine phosphorylation and increases in intracellular calcium (Ca2+i).2. ET‐1 stimulated DNA and protein synthesis and also increased cell number, but these mitogenic actions were small compared with those of EGF.3. ET‐1 and EGF increased the level of tyrosine phophorylation of a range of proteins with apparent molecular weights between 80 and 100 kDa and also increased phosphorylation of a single protein of 33 kDa.4. Ca2+i levels were increased by both ET‐1 and EGF. However, concentrations of EGF three orders of magnitude higher than those having mitogenic actions or increasing protein tyrosine phosphorylation were required. ET‐1 was a more potent stimulant of increases in intracellular calcium than of mitogenesis.5. We conclude that elevation of Ca2+i is unlikely to be an important signal for the mitogenic action of EGF. It is suggested that stimulants at the EGF receptor (EGF and transforming growth factor a) may play a role in the airway smooth muscle hyperplasia in asthma.
DIFFERENTIAL BLOCKADE OF THE RENAL VASOCONSTRICTOR AND DIURETIC RESPONSES TO ENDOTHELIN‐1 BY ENDOTHELIN ANTAGONIST
Authors: Kamphuis C. , Yates N. A. , McDougall J. G. 
Published: June 2007

SUMMARY1. The effect of cyclo(d‐Trp‐d‐Asp—Pro‐d‐Val—Leu) (or BQ123), a selective ETa receptor antagonist, on the vasoconstrictor and diuretic responses elicited by endothelin‐1 (ET‐1) was examined in conscious sheep with chronic indwelling renal arterial cannulae.2. Using low dose close renal arterial infusion, ET‐1 has potent effects on the kidney causing a marked decrease in effective renal plasma flow and an increase in urine output and free water clearance in the normally hydrated animal.3. The vasoconstrictor response to renal arterial infusion of ET‐1 at 5 μg/h was blunted by renal arterial infusion of the ETA receptor selective antagonist, BQ123 (400 μg/h).4. In contrast, the effect of ET‐1 on urine production and free water clearance was not affected by this dose of BQ123.5. The differential effect of BQ123 on renal blood flow and urine production suggests that these effects of endothelin on the kidney are mediated through different receptor mechanisms.
A NEW RESTRICTION FRAGMENT LENGTH POLYMORPHISM IN THE FIRST INTRON OF THE SPONTANEOUSLY HYPERTENSIVE RAT RENIN GENE
Authors: Wang D. Z‐M. , Wilks A. , Morgan T. O. , Nicolantonio R. Di 
Published: June 2007

SUMMARY1. Amplification of the entire first intron of the renin gene of spontaneously hypertensive rat (SHR), Wistar‐Kyoto (WKY) and Sprague‐Dawley rats (SD) followed by Bgl II digestion uncovered a new deletion (∼50 bp) which exists upstream of the SHR renin gene first intron tandem repeat element.2. The SHR tandem repeat element was 600 bp shorter than that in the WKY while the WKY tandem repeat element was 280 bp shorter than that in the SD.3. Since elements regulating gene expression are known to exist in the first intron of other genes, this new restriction fragment length polymorphism (RFLP) might play a role in the reported overexpression of the SHR renin gene independent of changes in the length of the tandem repeat element.
THE EFFECT OF ADRENALECTOMY ON WATER PERMEABILITY IN RAT PAPILLARY COLLECTING DUCT
Authors: Ray C. , Carney S. , Gillies A. 
Published: June 2007

SUMMARY1. Chronic adrenal insufficiency impairs maximal urine concentration, probably in part due to reduced medullary tonicity but also possibly by inhibition of distal nephron water transport. This latter defect has been demonstrated in rabbit but not in rat.2. Since the time between adrenalectomy and experiment was different in rabbit and rat studies, diffusional water permeability was evaluated in the papillary collecting duct in the absence and presence of submaximal (20 μU/mL) and supramaximal (200 μU/mL) arginine vasopressin (AVP) in adrenalectomized rats at 7, 14 and 21 days.3. Experimentation 7 days after adrenalectomy failed to demonstrate significantly altered basal or AVP‐induced water permeability which increased by 23 and 78% with submaximal and supramaximal concentrations, respectively. Submaximal AVP concentrations also induced a comparable change in water permeability in adrenalectomized rats at 14 days; however, 21 days after adrenalectomy, diffusional water permeability was not increased by 20 μU/mL AVP (3.31 ±.22 to 3.31 ±.24 μm/s). Nevertheless, the effect of a supramaximal AVP concentration (200 μU/mL) was not altered by adrenalectomy (4.54 ±.39 to 8.08 ±.96; P<0.01). Incubation of collecting ducts in aldosterone for 2 h did not reverse the inhibitory effect of chronic adrenalectomy on AVP‐stimulated water transport.4. These studies suggest that mineralocorticoid withdrawal does impair the hydro‐osmotic action of AVP in the rat papillary collecting duct but that this effect takes between 14 and 21 days to occur.
THE INTERACTION BETWEEN ENALAPRILAT AND SELECTED α‐ADRENOCEPTOR ANTAGONISTS IN ISOLATED RAT TAIL ARTERIES
Authors: Marwood John F. 
Published: June 2007

SUMMARY1. Isolated perfused rat tail artery preparations were used to investigate the effects of the angiotensin converting enzyme inhibitor enalaprilat on the actions of a series of α‐adrenoceptor antagonists. The agonist used was phenylephrine.2. Enalaprilat (1 μmol/L) potentiated the competitive α1‐adrenoceptor antagonist actions of phentolamine (10–100 nmol/L) and yohimbine (0.3–3.0 μmol/L) as well as the non‐competitive antagonist action of phenoxybenzamine (50–100 pmol/L).3. The competitive α1‐adrenoceptor antagonist action of prazosin (1–10 nmol/L) was not affected by enalaprilat.4. For the competitive α1‐adrenoceptor antagonists, including prazosin, there appeared to be an inverse relationship between antagonist potency and the extent of potentiation by enalaprilat.5. The results support the hypothesis and angiotensin II modulates vascular smooth muscle α1‐adrenoceptor function.
THE VASCULAR TISSUE ANGIOTENSIN I‐CONVERTING ENZYME ACTIVITY AND AORTIC ELASTIN CONTENT IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS FED FISH DIET
Authors: Murakami Tetsuo , Soga Masahiko , Mitsunaga Toshio , Yoshizumi Hajime , Ito Hiroyuki 
Published: June 2007

SUMMARY1. Stroke‐prone spontaneously hypertensive rats (SHRSP) were fed a diet with fish meal as the protein source (fish diet) during the progressive stage of hypertension, and its effects on the activity of angiotensin I‐converting enzyme (ACE) in serum and vascular tissues and on the aortic elastin content were studied. The effects of the antihypertensive drugs captopril and hydralazine were also studied.2. Stroke‐prone spontaneously hypertensive rats fed the fish diet showed a distinctly lower level (P<0.05) of serum ACE activity than the control group fed a commercial stock chow.3. ACE activity was enhanced in the SHRSP which was administered with captopril.4. Serum ACE activity was similar in the SHRSP receiving the hydralazine treatment and the control group.5. The thoracic aorta ACE activity was lowered more (P<0.05) in the fish diet group and the captopril‐treated group than in the control group. In the hydralazine‐treated group however, the activity was similar to the control group.6. The ratio of aorta weight to bodyweight was significantly lower (P<0.05) in the fish diet group and the captopril‐treated group than in the control group, but there was no difference in the hydralazine group. Higher levels of aortic elastin were observed in the drug‐treated groups (P<0.05).7. No differences were seen between the fish diet and captopril‐treated groups by electron‐microscopy.8. The results suggest that suppression of hypertrophy and ameliorations of reduction in elasticity of the vascular wall in the SHRSP fed a fish diet were due to inhibition of vascular tissue ACE activity.
ANGIOTENSIN II RECEPTOR DENSITY IN BOVINE OVARIAN FOLLICLES RELATES TO TISSUE RENIN AND FOLLICULAR SIZE
Authors: Nielsen A. H. , Hagemann A. , Svenstrup B. , Nielsen J. , Poulsen K. 
Published: June 2007

SUMMARY1. The purpose of this study was to investigate angiotensin II (AII) receptors in isolated bovine ovarian follicles and the relationship of their density to follicular concentrations of prorenin, active renin, oestradiol and progesterone.2. Displacement of [125I]‐[Sar1‐Ile5‐Ile8]‐AII binding by the AII receptor antagonists PD 123319 and Losartan (DuP 753) confirmed that follicular AII receptors are of subtype 2 (AT2 receptor).3. The dissociation constant (Kd) for [Ile5]‐AII (human AII) was 0.84 (range 0.51–1.47) nmol/ L. The receptor density varied between 90 and 5990 (mean 1640) fmol/ mg membrane protein.4. The follicular AII receptor density correlated positively with follicular diameter (Spearman's rho= 0.518; P<0.003) and tissue weight (Spearman's rho= 0.636; P<0.0001), and negatively with the active renin concentration in the follicular wall (Spearman's rho=‐0.399; P<0.02). The AII receptor density did not correlate with the follicular fluid concentrations of prorenin, active renin, oestradiol (E2, progesterone (P4) or the E2/P4 ratio. The follicular fluid concentrations of prorenin correlated negatively with the E2/P4 ratio (Spearman's rho= ‐0.716; P<0.00001).5. The inverse relationship between AII receptor density and the high active renin concentrations in the follicular wall suggests an active regulated tissue renin‐angiotensin system. A high AII receptor density is a general feature of large bovine ovarian follicles.
GABA RECEPTORS: AS COMPLEX AS ABC?
Authors: Johnston Graham A. R. 
Published: June 2007

SUMMARY1. Receptors for the inhibitory neurotransmitter GABA are currently classified pharmacologically into two major subtypes.2. GABAa receptors are antagonized by the convulsant alkaloid bicuculline, and are insensitive to activation by the GABA analogue baclofen. GABAB receptors are insensitive to bicuculline and activated stereoselectively by baclofen.3. There is increasing evidence for ‘novel’ GABA receptors that pharmacologically fall outside that defined by the GABAa/b classification.4. GABA receptors insensitive to both baclofen and bicuculline have been described in the spinal cord, optic tectum, retina, cerebellum and hippocampus. In addition such novel GABA receptors may be widespread in insects and bacteria. These novel receptors have been given a variety of descriptions: GABAc, GABAnanb (non‐A, non‐B) and GABAρ (cloned from retina).5. cis‐4‐Aminocrotonic acid (CACA), a structural analogue of GABA in a folded conformation, is considered to be a selective agonist of the putative GABAc receptors. Tritiated CACA binds to cerebellar membranes in a GABA‐sensitive, baclofen‐insensitive manner. It can be displaced only by relatively high concentrations of bicuculline.6. Autoradiographic studies show pronounced differences in regional distribution between the binding of CACA, the GABAa agonist muscimol and the GABAb agonist baclofen.7. Novel GABA receptors may represent important new pharmacological targets.
DIFFERENTIAL CONTROL OF VASCULAR TONE AND HEART RATE BY DIFFERENT AMINO ACID NEUROTRANSMITTERS IN THE ROSTRAL VENTROLATERAL MEDULLA OF THE RAT
Authors: Katahira K. , Mikami H. , Otsuka A. , Moriguchi A. , Kohara K. , Higashimori K. , Okuda N. , Nagano M. , Morishita R. , Ogihara T. 
Published: June 2007

SUMMARY1. To test the hypothesis that a central mechanism may play a role in the minimal reflex tachycardia noted in response to peripheral converting enzyme inhibition, we compared the effects of intravenous (i.v.) ceronapril (CER) with nitroglycerin (NTG) on neurotransmitter release in the rostral ventrolateral medulla (RVLM), using an in vivo microdialysis method in pentobarbital anaesthetized rats.2. CER (0.1 mg/kg, i.v.) caused a progressive decrease in glutamate (GLU) release (CER 65 ± 7%vs NTG 83 ± 3% of each baseline at 140 min, P<0.05) and attenuated the increase in glycine (GLY) release (CER 100 ± 8%vs NTG 122 ± 9%, P<0.05).3. Prevention of blood pressure reduction due to i.v. CER by concomitant infusion of a subpressor dose of angiotensin II (AII) attenuated the progressive reduction of GLU release (87 ± 4%, P<0.05 compared with NTG group), whereas GLY release was not affected (106±5%, NS compared with NTG group).4. Perfusion of GLU into this area at approximately physiological concentrations resulted in a sustained tachycardia with an attenuation of the depressor effect of i.v. CER and perfusion of GLY solely lowered blood pressure.5. These results demonstrate that i.v. converting enzyme inhibitor reduces the release of GLU in the RVLM, which was specifically caused by reducing circulating AII, without any effect on GLY release, thus resulting in the reduction of blood pressure with minimal effect on the heart rate.
BLOCKADE BY INTRAVENOUS LOSARTAN OF AT1 ANGIOTENSIN II RECEPTORS IN RAT BRAIN, KIDNEY AND ADRENALS DEMONSTRATED BY IN VITRO AUTORADIOGRAPHY
Authors: Zhuo Jialong , Song Keifu , Abdelrahman Aly , Mendelsohn Frederick A. O. 
Published: June 2007

SUMMARY1. The in vivo inhibition of angiotensin II (AII) receptor binding in the rat brain, kidney and adrenal was investigated after intravenous administration of the AT1‐selective AII receptor antagonist losartan.2. Male Sprague‐Dawley rats were administered intravenously either vehicle, or losartan at doses of 1, 3 or 10 mg/kg. Plasma samples were collected and tissues removed at 1,2, 8 or 24 h after administration of the antagonist, The effects of losartan on AII receptor binding were assessed by quantitative in vitro autoradiography.3. Losartan significantly increased plasma renin activity (PRA) by six‐fold and nine‐fold at doses of 1 and 10 mg/kg, respectively (P<0.05). Plasma losartan concentrations rose from 0.83 μg/mL at 1 mg/kg to 46.5 μg/mL at 10 mg/kg 1 h after administration of the drug. Plasma renin activity returned to control, whilst losartan was undetectable 24 h after injection of the antagonist.4. In the brain, losartan produced a dose‐dependent inhibition of AII receptor binding to the brain structures which express exclusively, or predominantly, AT1 receptors both outside and within the blood brain barrier. By contrast, losartan did not affect binding to the nuclei which contain exclusively, or predominantly, AT2 receptors.5. In the kidney, losartan blocked AII receptor binding to all anatomical sites in a dose‐dependent manner. The inhibition peaked at 1 h and persisted beyond 24 h despite the fact that PRA had returned to control, and losartan was not detectable in the circulation. In the adrenal gland, where AT1 and AT2 receptors occur in both the cortex and medulla, losartan caused partial inhibition at both regions.6. These results indicate that losartan, administered intravenously at these doses, and/or its active metabolites, partially penetrate the blood brain barrier to selectively inhibit central AT1 receptors, and exert selective and prolonged blockade of AT1 receptors in peripheral target tissues.
POTASSIUM CHANNEL OPENERS AND OTHER REGULATORS OF KATP CHANNELS
Authors: Challinor‐Rogers Joanne L. , McPherson Grant A. 
Published: June 2007

SUMMARY1. Interest in ATP‐sensitive K (Katp) channels first arose when it was shown that hypoglycaemic sulphonylureas, such as glibenclamide, closed these channels in pancreatic p‐cells to cause insulin release. The demonstration that certain smooth muscle relaxants (K channel openers) may exert their actions through opening a similar channel in vascular smooth muscle fuelled further investigation of these channels and their physiological role in a variety of tissue types, including various types of smooth muscle, cardiac and skeletal muscle and neural and endocrine organ function.2. The K channel openers have a variety of potential therapeutic applications, including disorders of smooth muscle hyperreactivity, such as hypertension, and a great deal of research has focused on this field. More recently, attention has turned to the cardiac actions of these compounds and this area is discussed in detail. One of the current problems is the lack of selectivity of Katp channel regulators. However, there have been a number of recent encouraging reports suggesting that, under certain pathophysiological conditions, the action of the K channel openers may be enhanced, conferring upon them some degree of selectivity.3. A number of endogenous regulators of these channels have been identified, particularly in the category of endogenous openers of these channels. At present though, the physiological role of these channels and the endogenous regulators identified, is unclear.4. It is evident that, although advances have been made, much work is still required to increase our understanding and ultimately to allow selective pharmacological manipulation of these channels to become a therapeutic reality.
EFFECT OF INCREASED MYOCARDIAL CYCLIC GMP INDUCED BY CYCLIC GMP‐PHOSPHODIESTERASE INHIBITION ON OXYGEN CONSUMPTION AND SUPPLY OF RABBIT HEARTS
Authors: Weiss Harvey R. , Rodriguez Elizabeth , Tse James , Scholz Peter M. 
Published: June 2007

SUMMARY1. We tested the hypothesis that increasing myocardial cyclic GMP levels would reduce myocardial O2 consumption and areas of low O2 supply/consumption balance, using zaprinast, a selective cyclic GMP‐phosphodiesterase inhibitor.2. The study was conducted in three groups (vehicle, 10−‐3 and 3×10−‐3 mol/L zaprinast) of anaesthetized open‐chest New Zealand white rabbits (n = 24). Coronary blood flow (radioactive microspheres), arterial and venous O2 saturation (microspectrophotometry), O2 consumption, cyclic GMP content (competitive binding) and cyclic GMP‐phosphodiesterase activity (conversion of 3H‐cyclic GMP to 3H‐GMP) were determined.3. Agents were applied to a patch on the myocardial surface and did not cause significant haemodynamic changes, except for bradycardia in the vehicle and low dose group.4. The total myocardial cyclic GMP‐phosphodiesterase activity was 148 ± 14 while the zaprinast (10 μmol/L) inhibitable activity averaged 63 ± 8 pmol/mg protein per min. Cyclic GMP content was increased with increasing doses of zaprinast (vehicle, 4.308 ± 0.349 pmol/g; low dose zaprinast, 4.803 ± 0.279 and high dose zaprinast, 7.938 ± 1.304 pmol/g).5. Coronary blood flow was not different after treatment (198 ±11, 209 ± 10 and 153 ± 9 mL/min per 100 g for the vehicle, low and high dose zaprinast, respectively).6. Under control conditions, 48% of the small veins had O2 saturations below 50%. With zaprinast, this value was reduced to 19% for the low and 24% for the high dose.7. Average venous O2 saturation increased with zaprinast (49 ± 2%, 61 ± 3% and 59 ± 1%). Myocardial O2 consumption was decreased with increasing doses of zaprinast (15.0 ± 1.9, 11.2 ± 1.0 and 7.7 ± 0.7 mL O2/min per 100 g for the vehicle, low and high dose zaprinast, respectively.8. Thus, increasing the myocardial level of cyclic GMP with zaprinast was correlated with reduced cardiac O2 consumption and a reduced number of veins with low O2 saturations.
EFFECTS OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE IV INHIBITOR, Ro20,1724, ON PANCREATIC EXOCRINE SECRETION IN DOG
Authors: Iwatsuki K. , Ren L‐M. , Chiba S. 
Published: June 2007

SUMMARY1. The effects of the cyclic nucleotide phosphodiesterase (PDE) inhibitors, Ro20,1724, 3‐isobutyl‐1‐methylxanthine (IBMX), trifluoperazine (TFP) and amrinone on pancreatic exocrine secretion were investigated in anaesthetized dogs in comparison with those of secretin and cholecystokinin octapeptide (CCK‐8).2. Ro20,1724 (1–30 nmol/kg), IBMX (3–30 nmol/kg), secretin (0.01–0.1 pmol/kg) or CCK‐8 (0.1–1 pmol/kg) injected i.a. elicited a dose‐dependent increase in the secretion of pancreatic juice, but TFP and amrinone (up to 1 μmol/ kg) did not.3. The bicarbonate concentration in pancreatic juice was increased and the protein concentration was decreased by Ro20,1724, IBMX and secretin. Cholecystokinin octapeptide increased the protein concentration but did not alter the bicarbonate concentration.4. Ro20,1724 and IBMX elicited more than the respective additive secretory response when added together with secretin, although the stimulatory effects of CCK‐8 with Ro20,1724 and IBMX were additive.5. Ro20,1724 and IBMX increased cyclic AMP concentration but did not affect cyclic GMP concentration.6. These results suggest that Ro20,1724 and IBMX have secretory properties on pancreatic exocrine glands of the dog, which may be mediated through an increase in cyclic AMP subsequent to inhibition of PDE activity. Furthermore, pancreatic PDE enzymes in the dog may be mainly type IV.