bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIFFERENTIATION OF NORADRENERGIC AND DOPAMINERGIC NERVES IN THE RAT KIDNEY: EVIDENCE AGAINST SIGNIFICANT DOPAMINERGIC INNERVATION
Authors: McGrath B. P. , Lim A. E. , Bode K. , Willis G. L. , Smith G. C. 
Published: June 2007

SUMMARY1. In the rat kidney catecholaminergic nerve elements were identified by fluorescence histochemistry in perivascular plexuses around corticula arteries and juxtaglomerular arterioles and in medullary vascular bundles. Fluorescence was abolished in all areas 24 h after treatment with 6‐hydroxydopamine (6‐OHDA; 150 mg/kg i.v.). Protection of noradrenergic endings from destruction by 6‐OHDA was afforded by pretreatment with desipramine (DMI; 25 mg/kg i.p.) which restored fluorescence towards control levels. By semiquantitative analysis fluorescence was identical in juxtaglomerular regions but slightly reduced around larger vessels in (DMI + 6‐OHDA)‐treated rats when compared to controls.2. Changes in tissue noradrenaline content, but not dopamine content, paralleled the changes in nerve fluorescence. Noradrenaline content was 4.10 pmol/mg protein (s.e.m. =0.22, n= 32) in controls and was reduced by 90% to 0.40 pmol/mg (s.e.m. =0.05, n= 23) in 6‐OHDA‐treated and by 26% to 3.01 pmol/mg (s.e.m. = 0.21, n= 23) in (DMI + 6‐OHDA)‐treated rats. Kidney dopamine content was 0.38 pmol/mg protein (s.e.m. =0.05, n= 32) in controls and was reduced by 55% to 0.18 pmol/mg (s.e.m. =0.02, n=17) in 6‐OHDA‐treated and by 53% to 0.17 pmol/mg (s.e.m. =0.02, n= 23) in (DMI +6‐OHDA)‐treated rats.3. The renin response to haemorrhage was examined in pentobarbitone sodium‐anaesthetized rats as a test of functional integrity of renal nerves in the three groups. Progressive 1 ml haemorrhages (to total blood loss of 4 ml, 1.3% body weight) resulted in similar increases in plasma renin activity in controls and (DMI + 6‐OHDA)‐treated animals but the response was significantly attenuated in 6‐OHDA‐treated rats.4. Renal catecholaminergic nerves appear to be predominantly noradrenergic. It is doubtful if a significant intrarenal dopaminergic system exists in the rat.
INFLUENCE OF NICORANDIL, AN ANTIANGINAL AGENT, ON THE THERAPEUTIC AND TOXIC CARDIOVASCULAR ACTIONS OF OUABAIN IN THE ANAESTHETIZED DOG
Authors: Nakamura Yasuyuki , Akima Michitaka , Sakai Kazushige 
Published: June 2007

SUMMARY1. The effects of nicorandil were investigated on ouabain‐induced cardiovascular actions in pentobarbitone‐anaesthetized dogs. Nicorandil (500 μg/kg per h) and ouabain (100 μg/kg per h), alone and in combination, were infused intravenously to three groups of dogs.2. Nicorandil gradually decreased systemic blood pressure, pressure‐rate product, left ventricular systolic pressure, and coronary vascular resistance, but did not significantly affect heart rate, left ventricular dP/dt max, coronary blood flow, plasma electrolyte concentrations and ECG patterns.3. The lethal dose of ouabain was 122 μg/kg (s.e.m. = 3, n= 6) and the dose required to elicit ventricular premature beats was 63 μg/kg (s.e.m. = 3, n= 6).4. When nicorandil and ouabain were simultaneously infused intravenously, nicorandil did not affect either the lethal dose of ouabain or the dose required to produce ventricular premature beats, but it significantly inhibited the marked increases in coronary vascular resistance and systemic blood pressure induced by ouabain alone. Even in combination with nicorandil, ouabain maintained its own positive inotropic effect.5. The results indicate that the combination of ouabain with nicorandil may be beneficial in some conditions of angina pectoris.
STRUCTURE OF HUMAN RENIN AND EXPRESSION OF THE RENIN GENE
Authors: Morris Brian J. , Catanzaro Daniel F. , Hardman Judy , Mesterovic Nikola , Tellam Judy , Hort Yvonne , Bennetts Bruce H. , Shine John 
Published: June 2007

SUMMARY1. The amino acid sequence of human renin was identified for the first time. This was determined from the nucleotide sequence of exons in the human renin gene identified in a genomic library by recombinant DNA techniques.2. Examination of amino acid residues involved in the enzymatic hydrolysis by human renin of the unique Leu10‐Val11 bond of human angiotensinogen revealed features peculiar to this highly specialized aspartyl protease.3. The expression of the renin gene was examined with a hybridization probe for renin mRNA in sections and extracts of tissues. In the submandibular gland of mice renin mRNA, like renin, increased during development and in response to testosterone in females; sodium depletion increased renin mRNA in kidney.
DIFFERENTIAL BLOCKING EFFECTS OF PRAZOSIN AND YOHIMBINE ON PRESSOR RESPONSES TO NEURONALLY RELEASED AND EXOGENOUSLY ADMINISTERED NORADRENALINE IN THE PITHED RAT
Authors: Kimura T. , Suzuki S. , Satoh S. 
Published: June 2007

SUMMARY1. The effects of prazosin and yohimbine on pressor responses to sympathetic nerve stimulation and intravenous injections of noradrenaline, phenylephrine and clonidine were examined in pithed rats to determine the postjunctional location of α2‐adrenoceptors in the vascular smooth muscle.2. Prazosin antagonized the pressor responses to phenylephrine and to sympathetic nerve stimulation more effectively than the responses to noradrenaline and to clonidine.3. Yohimbine antagonized the pressor responses to noradrenaline and to clonidine more effectively than the responses to sympathetic nerve stimulation and to phenylephrine.4. These results suggest that α2‐adrenoceptors as well as α1‐adrenoceptors produce vasoconstriction in the rat vasculature and support the hypothesis that α1‐adrenoceptors are predominantly located within the neuroeffector junction in contrast to an extrajunctional location of α2‐adrenoceptors.
THE POSSIBLE INVOLVEMENT OF ADRENOCEPTORS IN THE INTESTINAL EFFECT OF MORPHINE IN MICE
Authors: Wong Chak‐Lam 
Published: June 2007

SUMMARY1. The inhibitory effect of morphine on intestine was observed by following the intestinal transit of a charcoal meal. This inhibitory effect of morphine was antagonized by naloxone.2. In addition, the inhibitory effect of morphine was also suppressed by prior administration of yohimbine and phentolamine. However, prazosin, a selective α1‐adrenoceptor antagonist, had no effect on the inhibitory effect of morphine on intestinal transit.3. Furthermore, prior administration of propranolol did not alter this effect of morphine.4. These adrenoceptor antagonists by themselves, at the doses used, had no effect on the rate of intestinal transit of a charcoal meal in mice.5. These results suggest that α2‐adrenoceptors may be involved in the intestinal effect of morphine while α1‐ and β‐adrenoceptors do not appear to play any significant role in this aspect of morphine action.
EFFECTS OF PHENOXYBENZAMINE ON RESPONSES TO SOME RECEPTOR AGONISTS AND CALCIUM IN VITRO
Authors: McPherson Grant A. , Krstew Elena , Malta Errol 
Published: June 2007

SUMMARY1. Noradrenaline‐induced contractions of the rabbit and rat isolated aorta and guinea‐pig spleen strips were inhibited by concentrations of phenoxybenzamine which did not affect responses to calcium. This may suggest a specific action on α‐adrenoceptors. However, analysis of noradrenaline concentration‐effect curves in guinea‐pig spleen indicated that 1 μmol/1 phenoxybenzamine should have reduced the available receptor population to 6% of control, but data from radioligand binding experiments on the same tissues using [3H]‐prazosin indicated a reduction of the receptor population to only 82% of control. The reduced responsiveness observed in the organ bath study after phenoxybenzamine pretreatment, whilst not apparently related to effects on voltage‐dependent calcium channels, could be due to the actions of phenoxybenzamine on other (non‐receptor) processes such as receptor‐operated calcium channels.2. Maximal contractile responses to histamine in rabbit isolated aorta but not those in guinea‐pig isolated ileal preparations, were depressed by concentrations of phenoxybenzamine which depressed responses to calcium. Phenoxybenzamine produced parallel rightward shifts of curves to carbachol in guinea‐pig ileal preparations but only depressed maximal responses to the agonist in higher concentrations which reduced responses to calcium.3. On the basis of the results obtained with calcium it is possible that the effects of phenoxybenzamine on receptor‐mediated responses could be produced through the actions of this antagonist at less specific sites such as voltage‐dependent calcium channels for histamine in rabbit aorta and carbachol in guinea‐pig ileum. For α‐receptor mediated responses in aortic and splenic strip preparations and for histamine‐mediated responses in guinea‐pig ileum, the actions of phenoxybenzamine may reflect an interaction of the antagonist with receptor‐operated calcium channels.
RELAXATION FOLLOWING CONTRACTION IN TONICALLY CONTRACTED SMOOTH MUSCLE FROM THE BOVINE TRACHEA
Authors: Clarke Hilary M. , Kirkpatrick C. T. 
Published: June 2007

SUMMARY1. Isometric tension was recorded from strips of bovine tracheal smooth muscle in which the tone had been artificially raised by agonist drugs such as histamine and carbachol.2. Application of exogenous acetylcholine produced a biphasic response consisting of an initial contraction followed by a more prolonged relaxation before tone was restored to normal.3. Atropine blocked both components of the biphasic response to exogenous acetylcholine.4. Tetrodotoxin blocked neither phase of the response to exogenous acetylcholine even though a similar biphasic response to electrical stimulation was severely disrupted.5. Application of exogenous substance P produced a biphasic response of similar magnitude and form to that produced by acetylcholine.6. Application of exogenous histamine (tone raised by carbachol) also produced a biphasic response although higher concentrations were required to produce a relaxation of equal magnitude to that produced by acetylcholine.7. It is concluded that the inhibitory component of the biphasic response to exogenous acetylcholine occurs as a non‐specific sequel to contraction.
EFFECTS OF OPIOIDS ON THE ACH‐INDUCED CONTRACTION OF THE TOAD RECTUS
Authors: Sim M. K. , Ramabadran K. 
Published: June 2007

SUMMARY1. The inhibitory effect of morphine, nalorphine, oxymorphone, naloxone, naltrexone, N‐methylnaloxone, levorphanol, levallophan, dextrorphan, dextrallophan, levo‐methadone, dextro‐methadone, pethidine, leu‐enkephalin and U‐50 488 on the acetylcholine (ACh)‐induced contraction of the toad rectus was investigated.2. The dose‐response curves obtained in the absence and presence of increasing concentrations (0.1–3.2 or 10–320 μmol/l) of each opioid were subjected to three types of inhibition model discrimination, namely competitive, noncompetitive and uncompetitive.3. The results show that the opioids, except morphine, nalorphine and levorphanol, inhibit the ACh‐induced contraction by multiple modes of action. Except for the morphinans, the opioids inhibit competitively indicating that they are able to compete with ACh for cholinergic receptors at the nicotinic site.4. The opioids also inhibit noncompetitively (except oxymorphone and N‐methylnaloxone) and uncompetitively (except oxymorphone) indicating the possible existence of separate opioid binding sites and the combination of the opioids with the ACh receptor complex, respectively.5. The effect of morphine and levorphanol on the ACh‐induced contraction varies with the concentration of the two opioids. At concentrations below 80 μmol/l both opioids tend to inhibit the contraction while at concentrations of 80 μmol/l and above there is no apparent effect. Nalorphine has no effect on the contraction at the concentrations (10–320 μmol/l) employed in the study.6. An apparent structure‐activity relationship between the phenanthrenes and the various binding sites is noticeable; so also is the difference in the activity between the dextro and levo‐isomers of levorphanol and levallorphan indicating that the receptors exhibit stereospecificity.
INVESTIGATIONS INTO THE NATURE OF α2‐ADRENOCEPTORS IN RAT TAIL ARTERIES
Authors: Marwood J. F. , Chapman K. L. , Armsworth S. J. , Stokes G. S. 
Published: June 2007

SUMMARY1. In rat isolated perfused tail arteries, dose‐response curves were established for the vasopressor effects of phenylephrine (α1‐adrenoceptor agonist), clonidine (α1‐ and α2‐adrenoceptor agonist), clonidine in the presence of 10‐7 mol/l prazosin (α2‐agonist), and BHT‐920 (α2‐agonist).2. The ED50 values were: phenylephrine 1.85 × 10‐10 mol; clonidine 6.3 × 10‐10 mol; clonidine + prazosin 3.2 × 10‐6 mol; BHT‐920 6.1 × 10‐6 mol.3. The arterial reactivity to BHT‐920 was stable only after 4–5 h of perfusion.4. Responses to BHT‐920 were not antagonized by yohimbine (α2‐adrenoceptor antagonist) but were antagonized by low concentrations of prazosin (α1‐adrenoceptor antagonist).5. These data constitute conflicting evidence regarding the existence of α2‐adrenoceptors in rat tail arteries.6. The data are consistent with the proposal that there are two recognition sites on α1‐adrenoceptors; phenylephrine and BHT‐920 may stimulate different sites on α1‐adrenoceptors.
MECHANISM OF ACTION OF NATRIURETIC FRACTION OF URINE
Authors: Chakravarty Bhaskar J. , Gillies Alastair H. B. , Carney Shane L. 
Published: June 2007

SUMMARY1. The nature of calcium dependence of natriuretic fraction (NF)‐induced contractions in the rat smooth muscle anococcygeus and a possible correlation between the effect of NF on sodium transport and its natriuretic potency was investigated.2. NF and noradrenaline‐induced contractions were partially dependent on external calcium concentration. Ouabain and potassium (K) free solution (KoPSS)‐induced contractions were totally dependent on external calcium and were more effectively inhibited by calcium antagonists than those of NF and noradrenaline suggesting pharmacomechanical coupling as the mode of calcium dependence of NF.3. Like other agonists which contract by pharmacomechanical coupling, NF stimulted sodium transport (86rubidium uptake) in dog saphenous vein. Such stimulation correlated positively (r= 0.495, n= 17, P<0.05) with the natriuretic potency of NF.4. NF, like noradrenaline, contracts smooth muscle by pharmacomechanical coupling and NF‐induced natriuresis is associated with stimulation of the sodium pump.
ISOLATION OF GENOMIC CLONES CODING FOR THE HEAVY CHAINS OF TWO HUMAN CARDIAC MYOSINS
Authors: Catanzaro Daniel F. , O'Connell Anita M. , Morns Brian J. 
Published: June 2007

SUMMARY1. A 14 kilo‐base pair DNA clone (λHCMHC8) was isolated from a human genomic library by hybridization with a complementary DNA coding for a rabbit cardiac myosin heavy chain.2. λHCMHC8 hybridized to RNA isolated from cardiac but not skeletal muscle and formed heteroduplexes with a genomic clone coding for the fast type of rabbit cardiac myosin heavy chain. λHCMHC8 represented at least the 3′ half of the gene and contained over 11 exons which together spanned 4 kb of the coding region estimated to be 6 kb.3. Probes made from λHCMHC8 were used to rescreen the library in order to isolate overlapping clones and so extend the sequence (estimated to be approximately 25 kb for the whole gene, including introns). In addition, a clone having a different restriction map was isolated suggesting that man, like rat and rabbit, has two cardiac myosin heavy chain genes. These may code for proteins having different ATPase activity and be expressed in different proportions in different cardiac states, including hypertension.
CHARACTERIZATION OF THROMBOXANE A2 RECEPTORS IN THE HUMAN FETAL PLACENTAL VESSELS AND UMBILICAL VEIN
Authors: Boura A. L. A. , M N. , King R. G. , Mak K. K. ‐W. , Waltere W. A. W. 
Published: June 2007

SUMMARY1. An in vitro examination has been made of the thromboxane A2 receptors in human fetal placental villous vessels and umbilical veins utilizing the TxA2 agonist U46619 and its competitive antagonist AH22921.2. U46619 was a potent constrictor of both preparations. The EC50 were 25.3 nmol/1 (s.e.m. =2.5, n= 8) for causing constriction of perfused villous vessels and 22 nmol/1 (s.e.m. = 5, n= 17) for contraction of the venous longitudinal strip.3. AH22921 competitively antagonized responses to U46619 in both preparations. The pA2 values were not significantly different and their 95% confidence limits, obtained for its ability to antagonize responses to U46619 in villous vessels and the umbilical vein, were 8.0 (7.3‐8.8) and 7.1 (6.3‐7.9) respectively.4. It is concluded that TxA2 receptors in both the human fetal placental villous vessels and umbilical vein may be similar. They also may be similar to those in human platelets and pulmonary blood vessels.
MECHANISMS OF CAPTOPRIL‐INDUCED POTENTIATION OF THE DEPRESSOR RESPONSES TO ARACHIDONIC ACID IN RATS
Authors: Hui S‐C. G. , Dai S. , Ogle C. W. 
Published: June 2007

SUMMARY1. The mechanisms underlying potentiation by captopril of the depressor responses to arachidonic acid were studied in chloralose‐anaesthetized rats.2. Captopril, in a dose (0.5 mg/kg, i.v.) which inhibited the pressor responses to angiotensin I (0.03‐1 μg/kg, i.v.), enhanced the depressor responses to bradykinin (3‐300 μg/kg, i.v.) and potentiated the hypotensive action of arachidonic acid (3 mg/kg, intravenously). This phenomenon was observed not only when captopril and arachidonic acid were administered intravenously, but also when these compounds were injected directly into the aortic arch.3. The enhancement of arachidonic acid‐induced hypotension by captopril was not significantly affected by pretreatment with a low dose of aprotinin (3 mg/kg, i.v.), but was abolished by bilateral nephrectomy or by pretreatment with a higher dose of aprotinin (6 mg/kg, i.v.).4. It is suggested that captopril augments the depressor responses to arachidonic acid by inhibiting angiotensin converting enzyme. This results in accumulation of bradykinin which in turn increases release of vasodilator prostaglandins, originating most probably, from the kidneys. The possibility that blockade of angiotensin II formation by captopril may leave the vasodilator action of prostaglandin unopposed cannot be excluded.
CHARACTERIZATION OF SUBSTANCE P‐INDUCED BRONCHOCONSTRICTION IN THE GUINEA‐PIG: A COMPARISON WITH ACETYLCHOLINE
Authors: Stewart A. G. , Fennessy M. R. 
Published: June 2007

SUMMARY1. Substance P (0.5‐8.0 μg/kg, i.v.) induced bronchoconstriction in anaesthetized, mechanically‐ventilated guinea‐pigs, comprising increases in airways resistance and decreases in dynamic compliance.2. These bronchoconstrictor responses were unaffected by bilateral vagotomy, pretreatment with pheniramine (2 mg/kg, i.v.) or by pretreatment with atropine (100 μg/kg, i.v.). Acetylcholine‐induced (4‐32 μg/kg, i.v.) bronchoconstriction was prevented by atropine pretreatment, whereas bilateral vagotomy inhibited responses to acetylcholine.3. Ganglionic blockade using hexamethonium (20 mg/kg, i.v.) potentiated both substance P and acetylcholine on airways resistance and dynamic compliance.4. Indomethacin (1 or 5 mg/kg, i.v.) did not affect substance P‐induced bronchoconstriction, whereas the higher dose enhanced acetylcholine‐induced increases in airways resistance. In addition, aspirin pretreatment (20 mg/kg, i.v.) did not alter the bronchoconstrictor potency for either substance P or acetylcholine. On the other hand, the combined cyclo‐oxygenase/lipoxygenase inhibitors eicosatetraynoic acid (ETYA, 20 mg/kg, i.v.) and BW755C (20 mg/kg, i.v.) potentiated both acetylcholine and substance P on airways resistance and dynamic compliance.5. The results suggest that substance P‐induced bronchoconstriction may be modulated by the sympathetic nervous system and does not appear to be influenced by vagal or histaminergic mechanisms. The failure of indomethacin or aspirin to affect substance P‐induced bronchoconstriction, together with the enhancing effects of ETYA and BW755C pretreatments, provide evidence consistent with the existence of a bronchodilator mechanism which may be inhibited by compounds inhibiting lipoxygenase enzymes.
PLASMA AND BILIARY DISPOSITION OF PIRENZEPINE IN MAN
Authors: Lee S. P. , Paxton J. W. , Choong Y. S. 
Published: June 2007

SUMMARY1. The binding of pirenzepine, a selective muscarinic receptor antagonist to plasma and bile, was studied in vitro and in vivo. Plasma and hepatic bile were incubated with 14C‐pirenzepine and the bound fraction of 14C‐pirenzepine determined by equilibrium dialysis. The bound fractions were 12.6% (s.e.m. = 1.5) and 12.1% (s.e.m.= 1.6) in plasma and bile samples, respectively. After in vitro incubation, the radioactivity in both plasma and bile was removed by exhaustive dialysis against water for up to 94 h, suggesting that the binding was a noncovalent association.2. 14C‐Pirenzepine was also given intravenously to five postoperative patients with T‐tube drainage of hepatic bile. In plasma, 12.6% (s.e.m. = 1.8) of 14C‐pirenzepine was reversibly bound to albumin. By contrast, in bile 13.4% (s.e.m. = 3.2) was irreversibly bound, mainly to bilirubin glucuronides (>90%).3. After an intravenous injection of 14C‐pirenzepine, the radioactivity in plasma decreased bi‐exponentially with an initial distribution half‐life of 0.24 h and an elimination half‐life of 10.2 h. The radioactivity reappeared cyclically in bile, suggesting enterohepatic recirculation of 14C‐pirenzepine.
EFFECTS OF CAPTOPRIL ON THE SLEEP EEG OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Sim M. K. , Hutchinson J. S. , Chua M. E. 
Published: June 2007

SUMMARY1. Intracerebroventricular captopril produces significantly different effects on the sleep electroencephalogram (EEG) of normotensive Wistar‐Kyoto (WK) and spontaneously hypertensive rats (SHR).2. The compound produces a definite pattern of decrease in the percentage and power of the lower frequency EEG of the SHR. Corresponding action on the WK was confined to a general decrease in the power of the EEG.3. These findings suggest that certain components of the central renin‐angiotensin system in the SHR are abnormal.
HYPERTENSION ALTERS SLOPE AND RANGE BUT NOT SENSITIVITY TO VASOCONSTRICTOR AND VASODILATOR AGENTS IN THE RABBIT HINDQUARTER
Authors: Wright C. E. , Angus J. A. , Korner P. I. 
Published: June 2007

SUMMARY1. The vascular reactivity (slope and range) and location parameter (ED50) of dose‐response curves in the hindquarter vascular bed in conscious rabbits previously subjected to renal cellophane wrapping or sham operation were examined.2. The animals were instrumented with pulsed Doppler flow transducers and chronic indwelling aortic catheters for intra‐arterial drug infusion. The rabbits were ganglion‐blocked with mecamylamine before constructing full dose‐response curves to intra‐arterial infusions of methoxamine, noradrenaline, angiotensin II, acetylcholine, adenosine and serotonin.3. Curves relating dose to conductance were fitted to the experiments involving constrictors and curves relating dose to vascular resistance fitted to those involving dilator drugs. With both classes of drugs the reactivity was significantly higher in the hypertensive animals than in sham‐operated rabbits.4. There was no difference in sensitivity (ED50 value) between the hypertensive and control animals for any agonist tested.5. The increased reactivity, but not sensitivity, could be entirely accounted for by the vascular amplifier action of medial hypertrophy in hypertension.