bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tachykinin Receptors Mediating Contractions Of Oestrogen‐Primed Rat Uterus: Classification Using Non‐Peptide Antagonists
Authors: Fisher L , Pennefather Jn 
Published: March 2003

SUMMARY1. The aim of the present study was to characterize the tachykinin receptors mediating contractions of the uterus from the oestrogen‐primed rat. Apparent pKB values versus mammalian tachykinins and some subtype‐selective agonists were determined for the non‐peptide NK1, NK2 and NK3 receptor antagonists SR 140333, SR 48968 and SR 142801, respectively.2. Apparent pKB values for SR 48968 tested at concen‐ trations of 3, 10 and 30 nmol/L versus neurokinin (NKA, [Lys
5MeLeu
9Nle
10] NKA(4–10) and [Nle
10] NKA(4–10) were 8.79, 9.44 and 9.33, respectively, indicating activation of an NK2 receptor and, in the case of NKA, the possible activation of an additional receptor subtype. SR 48968 (30 nmol/L) did not affect responses to NKB (1 μmol/L), senktide (30 nmol/L), substance P (SP; 100 nmol/L) or [Sar
9Met(O2)
11] SP (100 nmol/L), indicating its selectivity at this concentration.3. SR 140333 (1–100 nmol/L) reduced the effects of the NK1‐preferring agonists SP and [Sar
9Met(O2)
11] SP, indicating the presence of NK1 receptors. The pKB estimate versus [Sar
9Met(O2)
11] was 9.01. SR 140333 (100 nmol/L) did not affect responses to NK2 and NK3 receptor‐preferring agonists.4. SR 142801 (100 nmol/L to 1 μmol/L) produced small rightward shifts in the log concentration–response curves to NKB, yielding an apparent pKB value of 7.0. At 1 μmol/L, SR 142801 reduced responses to the NK2 agonists, suggesting some non‐selectivity at this concentration.5. Taken together, these data provide strong evidence that tachykinin‐induced contractions of the uterus of the oestrogen‐primed rat are mediated by NK2 receptors, with some contribution from NK1 receptors.
MEDICAL SIGNIFICANCE OF CARDIOVASCULAR FUNCTION IN HIBERNATING MAMMALS
Authors: Wang SHI‐QIANG , Zhou ZENG‐QUAN 
Published: March 2003

SUMMARY1. The hibernating mammals inherited a stable cardiovascular function as a result of adaptation to extreme external and internal environments during hibernation.2. The cardiovascular function of a hibernator is characterized by three distinct features: (i) tolerance of hypothermia; (ii) resistance to dysrhythmia; and (iii) endurance of hypoxia. All these have clinical relevance in cardiovascular disorders in humans.3. We suggest that the hibernating mammal can serve as a useful animal model for research into the cardiovascular system.
SELECTIVE EFFECTS OF LOMERIZINE, A NOVEL DIPHENYLMETHYLPIPERAZINE Ca2+ CHANNEL BLOCKER, ON CEREBRAL BLOOD FLOW IN RATS AND DOGS
Authors: Hara Hideaki , Shimazawa Masamitsu , Sasaoka Masaaki , Yamada Chikaomi , Iwakura Yasushi , Sakai Takanori , Maeda Yu , Yamaguchi Takafumi , Sukamoto Takayuki , Hashimoto Munehiro 
Published: March 2003

SUMMARY1. In the present study we examined the effects of a new Ca2+ channel blocker (lomerizine), an antimigraine drug, on cerebral cortical blood flow (CBF) in anaesthetized rats (laser Doppler flowmetry) and on vertebral blood flow in anaesthetized beagle dogs (electromagnetic flowmeter).2. Lomerizine (1.25–10 mg/kg, p.o.) dose‐dependently increased CBF in rats without affecting blood pressure (BP) or heart rate (HR).3. The plasma concentration of lomerizine (free base) in anaesthetized rats at 30 and 60 min after the initial administration of 5 mg/kg, p.o., times at which there was a significant increase in CBF, was similar to that reported in healthy subjects receiving lomerizine at 10 mg (2 × 5 mg)/day, p.o., a dose that significantly reduces the frequency and mean duration of headache attacks.4. Flunarizine (10 mg/kg, p.o.) did not increase CBF significantly. Flunarizine (20 mg/kg, p.o.) did not increase CBF, but did decrease BP 30–120 min after its administration.5. Lomerizine (2.5 and 5 mg/kg, intraduodenally) dose‐ dependently increased vertebral blood flow in dogs without significantly changing BP or HR. With 10 mg/kg intraduodenal lomerazine, vertebral blood flow remained elevated from 20 to 240 min after administration and BP was decreased from 20 to 120 min.6. Thus, lomerizine had a greater effect on CBF than on BP and HR and, therefore, it may be clinically effective in con‐ditions associated with circulatory disturbances in the brain, such as migraine, without producing systemic effects (e.g. hypotension) generally seen with other Ca2+ channel blockers.
Glycopyrrolate Treatment Of Drooling In An Adult Male Patient With Cerebral Palsy
Authors: Neverlien Po , Sorumshagen L , Eriksen T , Grinna T , Kvalshaugen H , Lind A‐B 
Published: March 2003

SUMMARY1. The aim of the study was to assess the effect of glycopyrrolate on drooling in an adult male patient with cerebral palsy.2. After a thorough medical examination and consent in writing by the responsible guardian, a baseline sum score for frequency and seriousness of drooling was established over a 2 week period in addition to data on shifts of handkerchiefs, urination, defecation and observation of behaviour. Glycopyrrolate (1 mg) tablets were then administered, starting with one tablet daily the third week and increasing the daily dose by one tablet per week until a maximum of four tablets during week six and 4 days of week seven when the daily dose was reduced to two tablets for 3 days. For the four weeks 8–11 three tablets were given daily. In week 12 the dose was reduced to two tablets and for the weeks 13–15 no tablets of glycopyrrolate were given.3. For as long as the patient received three to four tablets of glycopyrrolate daily, drooling was markedly reduced and handkerchiefs were not necessary on some days. After the tablets were withdrawn drooling increased to approximately the same level as it was before treatment. No adverse medical, psychological, or social effects were observed.4. For shorter periods, glycopyrrolate can be given in controlled doses provided that an adequate medical assessment has been undertaken.
Inhibition Of Kinin Degradation On The Luminal Side Of Renal Tubules Reduces High Blood Pressure In Deoxycorticosterone Acetate Salt‐Treated Rats
Authors: Nakajima Shinichi , Ito Hiroshi , Hayashi Izumi , Kuribayashi Yoshikazu , Okumura Toshiaki , Yajima Yoshitada , Katori Makoto , Majima Masataka 
Published: March 2003

SUMMARY1. To determine whether the antihypertensive response in deoxycorticosterone acetate (DOCA) salt‐treated rats was mediated by kinins on the luminal side of renal tubules or in the circulation, selective urinary kininase inhibitors were administered to normal Brown Norway Kitasato (BN‐Ki) rats and kininogen‐deficient Brown Norway Katholiek (BN‐Ka) rats.2. Kinins were degraded by neutral endopeptidase (NEP) and carboxypeptidase Y‐like kininase (CPY) in urine, but were inactivated mainly by angiotensin‐converting enzyme (ACE) in the plasma.3. Ebelactone B inhibited CPY, while poststatin inhibited CPY and NEP.4. Daily administration of poststatin (5 mg/kg per day, s.c.) for 3 days reduced blood pressure (BP) in DOCA salt‐treated BN‐Ki rats, but not in BN‐Ka rats.5. Ebelactone B (5 mg/kg per day, s.c.) also reduced BP in BN‐Ki rats, which was accompanied by increased urinary sodium excretion, but had no effect on BP in BN‐Ka rats.6. Lisinopril (5 mg/kg per day, s.c.) had no effect on BP in either rat strain.7. Arterial kinin levels in BN‐Ki rats increased significantly (2.2–4.6 pg/mL) with captopril (10 mg/kg, s.c.). However, arterial kinin levels that induced hypotension following the infusion of bradykinin (1000 ng/kg per min, i.v.) were 110‐ fold higher than endogenous arterial kinin levels attained following captopril.8. These results suggest that inhibition of kinin degradation on the luminal side of the renal tubules may effectively attenuate hypertension.
Circumventricular Organs: Definition And Role In The Regulation Of Endocrine And Autonomic Function
Authors: Ganong William F 
Published: March 2003

SUMMARY1. The circumventricular organs (CVO) are structures that permit polypeptide hypothalamic hormones to leave the brain without disrupting the blood–brain barrier (BBB) and permit substances that do not cross the BBB to trigger changes in brain function.2. In mammals, CVO include only the median eminence and adjacent neurohypophysis, organum vasculosum lamina terminalis, subfornical organ and the area postrema.3. The CVO are characterized by their small size, high permeability and fenestrated capillaries. The subcommissural organ is not highly permeable and does not have fenestrated capillaries, but new evidence indicates that it may be involved in the hypertension produced by aldosterone acting on the brain.4. Feedback control of corticotropin‐releasing hormone (CRH) secretion is exerted by free steroids diffusing into the brain, but substances such as cytokines and angiotensin II act on CVO to produce increases in CRH secretion. Gonadal steroids also diffuse into the brain to regulate gonadotrophin‐releasing hormone secretion. Thyrotropin‐releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion.
Angiotensin Ii Modulation Of The Arterial Baroreflex: Role Of The Area Postrema
Authors: Bishop Vernon S , Sanderford Max G 
Published: March 2003

SUMMARY1. Resetting the operating point of the arterial baroreflex appears to be an important factor involved in determining the level of sympathetic outflow.2. Substantial data indicate that circulating angiotensin (Ang)II can reset the arterial baroreflex to higher operating pressures.3. This action of AngII to increase the level of sympathetic nervous system outflow relative to blood pressure may contribute to elevated mean arterial pressure (MAP) during AngII hypertension, as well as to the maintenance of MAP during low sodium states.4. In most instances, the resetting observed during elevated peripheral AngII is dependent on the area postrema (AP).5. Although the central mechanisms by which the arterial baroreflex resets to different operating pressures remain to be completely defined, the AP may provide a separate mechanism whereby humoral factors can modulate the operating point of the arterial baroreflex.
Cardiovascular Effects Of Chronic Nitric Oxide Synthase Inhibition In Genetically Hypertensive Rats
Authors: Orange Stefan J , Ledingham Janet M , Laverty Richard 
Published: March 2003

SUMMARY1. The possible role of an endothelial defect in the hypertension of the New Zealand genetically hypertensive (GH) rat strain was assessed by examining cardiovascular responses to the nitric oxide synthase (NOS) inhibitor Nω‐nitro‐
L‐arginine methyl ester (
L‐NAME) and the endothelium‐dependent depressor agent acetylcholine (ACh). The vascular sensitivity of the hindquarter to nitric oxide (NO) was examined using the NO donor sodium nitroprusside (SNP).2. NG‐Nitro‐
L‐arginine methyl ester (10 mg/kg per day in drinking water) was given to GH and normotensive (N) rats from age 7–9 weeks, with GH and N untreated control groups. Systolic blood pressure (tail‐cuff) was monitored weekly from age 5–9 weeks. At age 9 weeks, pressure responses to various vasoactive agents were measured in vivo and in the rat isolated hindquarter. Left ventricular (LV) mass was measured at the time of death.3. NG‐Nitro‐
L‐arginine methyl ester induced a greater hypertensive effect in GH (P < 0.001) compared with N (P < 0.05) rats and caused a significant increase in hindquarter perfusion pressure in GH rats only (P < 0.01).4. Genetically hypertensive rats had LV hypertrophy that was exacerbated by L‐NAME (P < 0.01). Left ventricular hypertrophy was not induced by
L‐NAME in N rats.5. The normalized response to ACh did not differ between GH and N control rats and was unaffected by L‐NAME treatment in vivo and in vitro except at the highest ACh dose (3 μg/kg) in GH hindquarters (P < 0.01). The response to SNP was similar in GH and N hindquarters and enhanced by
L‐NAME in GH (0.1 μg; P < 0.05) and N rats (0.01 μg, P < 0.01; 0.1 μg, P < 0.001).6. These results suggest that the L‐arginine/NO system is not deficient in GH rats and that endothelial function in the GH hindquarter is preserved. They confirm that NO is involved in mediating blood pressure in GH and N rats and raise the possibility that a non‐NO‐mediated mechanism may underlie ACh‐induced vasodilation in GH and N.
Basilar Artery Remodelling In The Genetically Hypertensive Rat: Effects Of Nitric Oxide Synthase Inhibition And Treatment With Valsartan And Enalapril
Authors: Ledingham JM , Laverty R 
Published: March 2003

SUMMARY1. The structure of the basilar artery and the relationship of structure to blood pressure and ventricular hypertrophy was examined in genetically hypertensive (GH) rats, their control normotensive (N) Wistar strain, GH given the nitric oxide synthase (NOS) inhibitor, NG‐nitro‐
L‐arginine methyl ester (
L‐NAME) and GH given
L‐NAME and either valsartan or enalapril.2. Systolic blood pressure (SBP; tail‐cuff) was measured weekly from age 7–12 weeks. At the end of the experiment at 12 weeks, the basilar artery was fixed by perfusion and embedded in Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and stained and stereological analysis applied to quantify the morphology of the vessels. Left ventricular (LV) mass was determined.3. Both SBP and LV mass were significantly increased in GH compared with N (P < 0.001) and increased further in GH given
L‐NAME (P < 0.05). The GH
L‐NAME + valsartan and GH
L‐NAME + enalapril groups had significantly lower (P < 0.001) SBP and LV mass than the GH
L‐NAME group.4. Basilar arteries in GH (which are frankly hypertensive, but have no apparent endothelial defect) showed hypotrophic inward remodelling compared with the N control group with no change in media to lumen ratio.5. In the GH L‐NAME group, further inward remodelling occurred and the media to lumen ratio was increased compared with N (P < 0.01) and GH (P < 0.05). Valsartan treatment in GH
L‐NAME rats caused eutrophic outward remodelling. Enalapril caused hypertrophic outward remodelling, suggesting that the angiotensin II‐stimulated growth was not entirely suppressed with an angiotensin‐converting enzyme inhibitor or that there was a bradykinin effect with enalapril.6. In GH with an endothelial defect induced by treatment with L‐NAME, the further remodelling, together with an increased media to lumen ratio and the development of a stroke‐like syndrome, indicates the NOS‐inhibited GH rat may be a useful model for essential hypertension (where it is known that endothelial abnormalities exist) and where stroke can develop as a consequence of the hypertension.
Physiological Effects Of Extracellular Nucleotides In The Inner Ear
Authors: Housley Gary D 
Published: March 2003

SUMMARY1. Electrochemical homeostasis, sound transduction and auditory neurotransmission in the cochlea are influenced by extracellular purines and pyrimidines.2. Evidence that ATP and related nucleotides influence inner ear function arises from a considerable number of cellular, molecular and physiological studies in vitro and in vivo.3. With a full understanding of these processes, which include ionotropic (P2X receptor) and metabotropic (P2Y receptor) signal transduction pathways, signal termination involving ecto‐nucleotidases and recycling via nucleoside transporters, exciting possibilities emerge for treating hearing disorders, such as Menière’s disease, tinnitus and sensorineural deafness.
Mechanisms Of α,β‐Methylene ATP‐Induced Inhibition In Rat Ileal Smooth Muscle: Involvement Of Intracellular Ca2+ Stores In Purinergic Inhibition
Authors: Storr M , Franck H , Saur D , Schusdziarra V , Allescher H‐D 
Published: March 2003

SUMMARY1. In order to investigate purinergic effects on rat ileal smooth muscle, we used α,β‐methylene ATP (α,β‐MeATP), ATP, ADP and UTP. α,β‐Methylene ATP and ATP were the only agonists that caused a concentration‐dependent inhibition of carbachol‐precontracted smooth muscle. The inhibitory effect of α,β‐MeATP was completely blocked by pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (3 × 10–5 mol/L), a selective antagonist of the P2X > > P2Y receptor.2. Using reverse transcription–polymerase chain reaction we demonstrated the presence of both, P2X and P2Y receptor mRNA within the rat ileal longitudinal muscle/myenteric plexus layer preparation.3. The α,β‐MeATP‐induced inhibition was blocked in a concentration‐dependent manner in the presence of the K+ channel blocker apamin, but was unaffected by other K+ channel blockers, such as charybdotoxin (10–7 mol/L), 4‐aminopyridine (10–4 mol/L), glibenclamide (10–5 mol/L) and tetraethylammonium (10–3 mol/L).4. The α,β‐MeATP‐induced inhibition was unaffected by pretreatment with atropine (10–6 mol/L), phentolamine (10–6 mol/L), propranolol (10–6 mol/L), nitrendipine (10–7 mol/L), pertussis toxin (10–6 mol/L) NG‐nitro‐
L‐arginine (3 × 10–4 mol/L) and tetrodotoxin (10–6 mol/L), excluding an involvement of adrenergic, cholinergic, neural, nitrinergic or G‐protein involvement in purinergic‐mediated inhibition.5. In order to investigate whether the internal Ca2+ stores participated in the inhibitory effect observed, we depleted internal Ca2+ stores with cyclopiazonic acid, a specific Ca2+‐ATPase inhibitor. The inhibitory effect of α,β‐MeATP was completely abolished after depletion of the intracellular Ca2+ stores.6. This is in contrast with the effects seen for neurotensin, where neurotensin‐induced inhibition was unchanged after depletion of intracellular Ca2+ stores, suggesting at least two different pathways of apamin‐sensitive non‐adrenergic, non‐cholinergic inhibition in rat ileal smooth muscle.7. According to our results, the inhibitory effect of α,β‐MeATP in rat ileum longitudinal smooth muscle is mediated via a P2 purinoceptor, most likely a P2X receptor, involves G‐protein‐independent activation of an apamin‐sensitive K+ channel and requires filled intracellular Ca2+ stores.
Cardioprotective Effects Of Nicorandil In Rabbits Anaesthetized With Halothane: Potentiation Of Ischaemic Preconditioning Via KATP Channels
Authors: Nakae Ichiro , Takaoka Atsushi , Mitsunami Kenichi , Yabe Takahiro , Ito Makoto , Takahashi Masayuki , Matsumoto Tetsuya , Omura Tomoko , Yokohama Hiroshi , Kinoshita Masahiko 
Published: March 2003

SUMMARY1. The roles of ATP‐sensitive K+ channels (KATP channels) in ischaemic or pharmacological preconditioning in the rabbit heart remain unclear. Infarct limitation by ischaemic preconditioning was abolished by the KATP channel blocker glibenclamide under ketamine/xylazine anaesthesia, but not under anaesthesia induced by pentobarbital. Infarct limitation by the KATP channel opener pinacidil was detected under ketamine/xylazine anaesthesia, but not under pentobarbital anaesthesia. Thus, these effects appear to be anaesthetic dependent.2. In the present study, we examined whether nicorandil (a KATP channel opener nitrate) exhibits cardioprotective actions under halothane anaesthesia, another commonly used volatile anaesthetic. Control animals were subjected to 40 min coronary occlusion and 120 min reperfusion. Before 40 min ischaemia, the nicorandil group received nicorandil (100 μg/kg per min, i.v., for 10 min), the 5′ preconditioning (PC) group received 5 min ischaemia/20 min reperfusion, the 2.5′PC group received 2.5 min preconditioning ischaemia/20 min reperfusion, the nicorandil + 2.5′PC group received both nicorandil and 2.5 min ischaemia/20 min reperfusion, the nicorandil + 2.5′PC + 5‐hydroxydecanoate (5HD) group received both nicorandil and 2.5 min ischaemia/20 min reperfusion in the presence of 5‐hydroxydecanoate (5HD; a KATP blocker) and the 5HD group received 5 mg/kg, i.v., 5HD alone. Myocardial infarct size in control (n = 7), nicorandil (n = 5), 5′PC (n = 8), 2.5′PC (n = 5), nicorandil + 2.5′PC (n = 5), nicorandil + 2.5′PC + 5HD (n = 5) and 5HD (n = 4) groups averaged 44.4±3.6, 41.7±5.7, 17.8±3.2,* 34.1±4.8, 21.3±4.2,* 39.1±5.6 and 38.9±5.0% of the area at risk, respectively (*P < 0.05 vs control).3. Thus, nicorandil alone did not have an infarct size‐ limiting effect in halothane‐anaesthetized rabbits. However, the results suggest that even when nicorandil alone does not demonstrate a direct cardioprotective effect, it may enhance ischaemic preconditioning via KATP channels.
Electrophysiological Characteristics Of The Ca2+‐Activated Cl– Channel Family Of Anion Transport Proteins
Authors: Fuller Catherine M , Benos Dale J 
Published: March 2003

SUMMARY1. A protein isolated from the bovine tracheal epithelium behaves as a Ca2+‐activated Cl– channel (CaCC) when incorporated into planar lipid bilayers.2. An antibody raised against this protein was used to screen a cDNA expression library and resulted in the isolation of a cDNA clone that exhibited nearly identical electrophysiological characteristics to the isolated endogenous protein when expressed.3. Recent cloning of several related proteins has revealed that the cloned bovine CaCC is one of a large and growing family. All new family members so far examined are associated with the appearance of a novel Ca2+‐mediated Cl– conductance when heterologously expressed.4. This new group of proteins may underlie the Ca2+‐mediated Cl– conductance upregulated in the cystic fibrosis (CF) knockout mouse and thought to be responsible for the escape from the significant airway pathology associated with CF.
Species Differences In The Actions Of Sensory Neuropeptides On Contractility Of The Smooth Muscle Of The Rat And Guinea‐Pig Prostate
Authors: Ventura Sabatino , Lau Winnie Ak , Buljubasich Sretna , Pennefather Jocelyn N 
Published: March 2003

SUMMARY1. The present review describes the actions of sensory neuropeptides on the contractility of the rat and guinea‐pig prostate gland and discusses the differences in sensitivity of the smooth muscle of the prostates taken from these species to these neuropeptides.2. Nerve fibres immunoreactive for the tachykinins substance P and neurokinin A, as well as for the sensory neuropeptide calcitonin gene‐related peptide (CGRP), are sparsely distributed throughout the fibromuscular stroma of the prostate gland in both the rat and guinea‐pig.3. In functional experiments, tachykinin agonists potentiate electrical field stimulation‐induced contractile responses of prostates taken from guinea‐pigs, but have no effect on those taken from rats. This potentiation is through stimulation of tachykinin NK1‐receptors.4. Conversely, CGRP inhibits electrical field stimulation‐induced contractile responses of prostates taken from rats, but has no effect on those taken from guinea‐pigs.5. It is concluded that although the sensory innervation to the prostate glands of the rat and guinea‐pig appears similar, the nature and sensitivity of the contractile response of the prostatic smooth muscle to applied sensory neuropeptides is vastly different in the two species.