bluuebunny/crossref_metadata_2025 huggingface dataset:
POLYMERASE CHAIN REACTION‐BASED DNA FINGERPRINTING IN THE SPONTANEOUSLY HYPERTENSIVE RAT: POTENTIAL SOURCE OF cDNA LIBRARY PROBES
Authors: Di Nicolantonio Robert , Imai Takashi , Ikeda Katsumi , Sawamura Makoto , Yamori Yukio , Murakami Kazuo
Published: June 2007

1. Using the Polymerase Chain Reaction with a primer homologous to a repetitive unit found at irregular distances in the rat genome, we were able to synthesize DNA fragments spanning such units and visualize them as a ladder of discrete bands following electrophoresis.

2. Differences between fingerprint patterns generated using SHR, WKY and SD DNA, in the form of band deletions or duplications, were readily detected.

3. Unlike traditional fingerprinting, PCR fingerprints allow the ready extraction and characterization of polymorphic bands. Such bands could then be used as probes with which to screen a cDNA library that might, in turn, identify expressed genes involved in the development of hypertension.
THE HETEROGENEITY OF 11‐β‐HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN THE RAT HIPPOCAMPUS IMPLIES A COMPLEX REGULATION OF STEROID HORMONE ACTION
Authors: Smith R. E. , Mercer W. R. , Provencher P. H. , Obeyesekere V. , Krozowski Z. S.
Published: June 2007

1. The rat hippocampus 1l‐β‐hydroxysteroid dehydrogenase (11‐HSD) displays a different substrate specificity to that of other tissues. S1 nuclease analysis was used to determine whether the hippocampal messenger RNA is different from that found in other tissues.

2. SI nuclease analysis using probes spanning the full length cDNA demonstrated that there were no differences in sequence between the hippocampal 11‐HSD and the enzyme originally cloned from the liver.

3. These results suggest that there may be multiple 11‐HSD isoforms in the hippocampus with different substrate specificities.
DA‐1 RECEPTORS MEDIATE RENAL EFFECTS OF THE DOPAMINE PRODRUG, GLUDOPA, IN CONSCIOUS RABBITS
Authors: Wang Zhi‐Qin , Way Diana , Trigg Lisbeth , McGrath Barry P.
Published: June 2007

1. Eight male rabbits were implanted with Doppler flow probes around the lower abdominal aorta and left renal artery. A 2 week recovery period was allowed prior to the experiment.

2. Normal saline, gludopa at 25 μmg/kg per min and at 100 μg/ kg per min were each infused i.v. for 60 min. One week later the same protocol was administered to four of these animals in addition to DA‐1 antagonist SCH 23390 (0.3 mg/kg i.v.) before gludopa infusion.

3. Gludopa elicited significant increases in urine flow, urinary sodium excretion and renal blood flow, and decreased renal vascular resistance. These changes were abolished by the DA‐1 antagonist. Blood pressure, heart rate and hindlimb blood flow remained unchanged.

4. Urine dopamine excretion was increased 1200‐fold and 7800‐fold after gludopa administration at 25 μg/kg per min and 100 μg/kg per min, respectively, while plasma dopamine concentration and plasma renin activity (PRA) were not significantly altered. However, PRA was elevated by gludopa with DA‐1 antagonism.

5. The renal vasodilation, natriuresis and diuresis produced by gludopa in conscious rabbits appears to be mediated by locally generated dopamine via DA‐1 receptors.
COMPARISON OF PARATHYROID HORMONE AND CALCITONIN ON RAT RENAL CALCIUM AND MAGNESIUM TRANSPORT
Authors: Carney S. L.
Published: June 2007

1. Because in vitro adenylate cyclase activity studies suggest that parathyroid hormone (PTH) and calcitonin (CT) increase renal tubular calcium and magnesium reabsorption by stimulating the same transport mechanism, the separate and combined effects of these hormones on calcium and magnesium transport was assessed in the rat.

2. Fractional excretion of calcium was 9.5 ±0.5% in calcium‐infused thyroparathyroidectomized (TPTX) rats and was reduced to 5.1 ±0.6 and 4.1 ±0.6% by maximal hypocalciuric concentrations of PTH and CT, respectively.

3. Combined administration of maximal PTH and CT produced an effect on fractional and absolute calcium excretion similar to that recorded with maximal CT alone. The combined administration of half‐maximal concentrations of PTH and CT also produced a comparable fall in the fractional excretion of calcium to 3.0 ± 0.7%, which was similar to that observed in the ‘maximal CT’ and ‘maximal PTH plus CT’ groups. The magnesium reabsorption data were comparable.

4. These results support biochemical data suggesting that PTH and CT act upon the same transport site, presumably within the thick ascending limb of Henle's loop, to facilitate calcium and magnesium reabsorption.
CAPTOPRIL MAGNIFIES THE INCREASE IN ANGIOTENSIN I‐CONVERTING ENZYME ACTIVITY IN RATS WITH AMINONUCLEOSIDE NEPHROSIS
Authors: Pedraza‐Chaverri José , Maciel Avril H. , Cruz Cristino , Peña José Carlos
Published: June 2007

1. Serum, tissue and urine angiotensin I‐converting enzyme (ACE) activity was estimated in the following groups of rats: saline‐injected rats (controls); captopril‐treated (CAP) control animals (CONTROL‐CAP); puromycin aminonucleoside (PAN)‐induced nephrotic syndrome (NS); and CAP‐treated animals with NS (NS‐CAP).

2. Serum ACE activity increased in the CONTROL‐CAP, NS, and NS‐CAP groups. The increase in the NS‐CAP group was significantly higher compared with the NS or CONTROL‐CAP groups.

3. In the CONTROL‐CAP group, tissue ACE decreased in brain, heart and adrenal glands, and remained unchanged in the lung, testis, kidney, small intestine and liver. In the NS group, tissue ACE activity increased in the lung and testis, decreased in the brain and heart, and remained unchanged in the small intestine, adrenal glands, kidney and liver. Tissue ACE activity increased significantly in the NS‐CAP group compared with the other groups. This increase in tissue ACE may contribute to an increase in the serum ACE activity in the NS‐CAP group compared with the NS group.

4. Urine ACE activity increased in the NS and NS‐CAP groups, although the rise in the NS‐CAP group was significantly higher. The urine ACE correlated significantly with the circulating levels of this enzyme in the NS and NS‐CAP groups. The loss of ACE in the urine in the presence of an increased serum ACE activity indicates that the biosynthesis of tissue ACE and its release into the bloodstream must be elevated.
BRONCHODILATORY ACTIVITY AND PHARMACOKINETICS OF NEW XANTHINES IN GUINEA‐PIGS
Authors: Takagi Kenzo , Hasegawa Takaaki , Nadai Masayuki , Sakai Ryousuke , Miyamoto Kenichi
Published: June 2007

1. The in vitro biological activities and the effect of protein binding on the relaxant effects in vivo of N‐3‐alkylxanthine and N‐3‐alkyl‐N‐1‐methylxanthine derivative were investigated in guinea‐pigs.

2. A significantly positive correlation was observed among the in vitro muscle relaxant activity, the cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) inhibitory activity and the protein‐binding potency of xanthine derivatives. However, there was a weak relationship between these activities and affinity for adenosine receptors.

3. When theophylline, enprofylline and 1‐methyl‐3‐propylxanthine (MPX) were injected intravenously in guinea‐pigs, their ED50 values were 6.1, 3.3 and 1.0 mg/kg, respectively. Plasma concentrations of these drugs obtained following the intravenous injection of the ED50 approximated the theoretically effective concentration (EC50) predicted from both the relaxant effects in vitro and the protein binding parameters. A good linear correlation was observed between bodyweight in four species (rats, guinea‐pigs, rabbits and humans) and certain pharmacokinetic parameters of enprofylline and theophylline.

4. The present study indicates that differences in the relaxant effects of these drugs in vitro and in vivo can be explained in part by protein binding, and that the protein binding of these xanthine bronchodilators is an important determinant for their pharmacological activity. Guinea‐pigs provide a useful model for studying pharmacodynamic‐pharmacokinetic relationships of new bronchodilators.
A comparison of guanfacine, bunazosin, atenolol and nadolol on blood pressure and plasma noradrenaline responses to cold pressor testing
Authors: Koshiji Masatoshi , Ito Hiroyasu , Minatoguchi Shinya , Watanabe Hiroko , Imai Yoko , Kakami Masao , Hirakawa Senri
Published: June 2007

b

1. The role of the presynaptic adrenoceptor subtypes in man was investigated based on observation of the changes in blood pressure (ΔBP) and plasma noradrenaline concentration (ANA) with the cold pressor test (CPT).

2. The CPT was well reproducible for BP and NA when performed at a 2 week interval in patients with mild hypertension.

3. After administration for 4 weeks, guanfacine (Gf; (α‐adrenoceptor agonist) decreased the ΔNA response to CPT.

4. After administration for 2 or 4 weeks, bunazosin (Bu; α1‐adrenoceptor antagonist) atenolol (At; β1‐adrenoceptor antagonist) and nadolol (Nd; non‐selective β‐adrenoceptor antagonist) did not affect the ΔNA response to CPT.

5. Both Gf and Bu decreased the systolic blood pressure response (ΔSBP) to CPT after 4 weeks of the administration. Neither At nor Nd significantly changed the ΔSBP response to CPT.

6. It is likely that Gf stimulated the presynaptic α2 adrenoceptors at the sympathetic nerve endings as well as the central α2 adrenoceptors, inhibiting the release of noradrenaline. It is unlikely that Bu, At and Nd exerted any clearly defined action on the presynaptic adrenoceptors in human hypertensive subjects.
EFFECTS OF ACUTE SUPERIOR CERVICAL GANGLIONECTOMY ON CEREBRAL BLOOD FLOW AND METABOLISM IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS SUBJECTED TO CEREBRAL ISCHAEMIA
Authors: Nagao Tetsuhiko , Sadoshima Seizo , Ishitsuka Takao , Kusuda Kenji , Shiokawa Osamu , Lbayashi Setsuro , Fujishima Masatoshi
Published: June 2007

b

1. The effects of acute bilateral superior cervical ganglionectomy on cerebral blood flow and metabolism were investigated in stroke‐prone spontaneously hypertensive rats (SHRsp), before and during cerebral ischaemia.

2. The resting cerebral blood flow was comparable between the control and denervated animals.

3. There was no significant difference in cerebral blood flow or concentration of tissue energy metabolites (adenosine triphosphate [ATP], lactate and pyruvate) between the sham‐operated control and denervated animals during ischaemia.

4. The results suggest that sympathetic innervation of cerebral vessels originating from superior cervical ganglia may not play a major role in the progression of cerebral ischaemia in SHRsp.
THE EFFECT OF OVINE PROLACTIN ON THE EPIDIDYMAL SIALIC ACID CONCENTRATION IN MALE RATS
Authors: Gautam Rajeev , Pereira Ben M. J.
Published: June 2007

SUMMARY

1. Previous experiments have shown that the level of sialic acid in the epididymis is influenced by factors originating in the testis.

2. To exclude interference from these factors, both orchidectomized and duct‐ligated rats were used to study the potential role of prolactin in the epididymis.

3. When ovine prolactin was injected in orchidectomized rats, a dose‐related increase in the level of sialic acid was observed in the epididymis.

4. That this action of prolactin is independent of androgen was confirmed by studies using bromocryptine, which decreases circulating endogenous prolactin.

5. The physiological role(s) of epididymal sialic acid production in response to prolactin remain to be established.
AGEING HAS NO EFFECT ON THE VOLUME DENSITY OF HEPATOCYTES, RETICULOENDOTHELIAL CELLS OR THE EXTRACELLULAR SPACE IN LIVERS OF FEMALE SPRAGUE‐DAWLEY RATS
Authors: Martin G. , Sewell R. B. , Yeomans N. D. , Smallwood R. A.
Published: June 2007

1. The hepatic reticuloendothelial cell population is generally assumed to increase in size, along with the liver, during ageing in rats. However, this has not been rigorously established.

2. Using electron microscopy and stereological techniques, the present study has shown that the volume densities of hepatocytes and Kupffer cells (and probably also of endothelial cells, fat storing cells and the extracellular space) of the livers of female Sprague‐Dawley rats are the same at 2 and 24–25 months of age.

3. This result indicates that the increase in size of the liver during ageing in the rat is associated with an equivalent increase in the volume of each cell population and the extracellular space.
ATRIAL NATRIURETIC PEPTIDE IN PREGNANCY: RESPONSE TO ORAL SODIUM SUPPLEMENTATION
Authors: Lowe Sandra A. , Macdonald Graham J. , Brown Mark A.
Published: June 2007

1. The control of extracellular fluid volume (ECFV) in normal pregnancy may be related to changes in atrial natriuretic peptide. Previous studies in non‐pregnant subjects have suggested that plasma atrial natriuretic peptide (ANP) increases in response to dietary sodium supplementation because of an increase in plasma volume, although this has not been measured directly.

2. Nine women who were pregnant in the third trimester undertook oral sodium supplementation (136 mmol) for 5 days in addition to their usual diet. Twenty‐four hour urinary sodium excretion increased by 125 ± 54 mmol/day (mean ±s.d.; P < 0.01). Plasma volume was unchanged, although total ECFV tended to increase (P < 0.09 and bodyweight increased (1.3 ± 1.4 kg; P < 0.01) at the end of these diets.

3. Plasma ANP increased by 30.7 [8.6, 34.5] pmol/L (median [25th, 75th percentile]; P < 0.05), while plasma renin concentration decreased significantly from 7.3 [6.2, 11.2] to 2.6 [1.7, 3.9] pmol angiotensin I/mL (P < 0.01), as did plasma aldosterone concentration (1435 [1162,1722] to 753 [595, [110] fmol/mL; P < 0.01). Plasma vasoactive intestinal peptide was unchanged.

4. Pregnant women respond to increased dietary sodium with an increase in plasma ANP in the absence of a significant increase in plasma volume. The acute regulation of plasma ANP in response to increases in dietary sodium in pregnant women does not appear to be mediated by changes in intravascular fluid volume.
RESPONSIVENESS AND SENSITIVITY TO CHOLINERGIC AGONISTS AND ANTAGONISTS IN BOVINE ISOLATED BRONCHIAL MUSCLE
Authors: Matera Maria G. , Cazzola Mario , Constantino Maria , De Santis Dante , Rossi Francesco
Published: June 2007

1. Airways derived from different levels of the lung exhibit a difference in the reactivity and sensitivity to agonists. We have evaluated the effect of acetylcholine and cholinergic selective (pirenzepine, gallamine and 4‐dipherylacetoxymethyl piperidine [4‐DAMP]) and non‐selective (atropine) antagonists on bovine proximal and distal smooth muscle preparations.

2. The distal preparations are more sensitive to acetylcholine than proximal bronchi. The relaxant effect of three selective antagonists on the distal and proximal tissues was the same when the results for each drug were compared.

3. Atropine and 4‐DAMP were more potent than pirenzepine and gallamine in relaxing both proximal and distal bovine smooth muscle preparations.

4. These data suggest that the muscarinic sites on the smooth muscle of bovine airways are of the M3 subtype.
THE TISSUE RENIN‐ANGIOTENSIN SYSTEM AND ITS FUNCTIONAL ROLE
Authors: Johnston C. I. , Burrell L. M. , Perich R. , Jandeieit K. , Jackson B.
Published: June 2007

1. The components of the renin‐angiotensin system exist in many cardiovascular tissues (heart vessels, kidneys, adrenal glands).

2. Angiotensin‐converting enzyme (ACE) is similar in somatic cells from all these sites.

3. ACE contains two catalytic sites that have different conformation requirements. This suggests that each site may have different substrates and that specific inhibitors could be developed for each site.

4. The cardiovascular functions of tissue ACE may include the regulation of regional blood flow, modulation of local sympathetic activity, stimulation of hyperplasia and hypertrophy and the mediation of inflammation.
EFFECT OF ENVIRONMENTAL AND HYPOTHALAMIC FACTORS ON THYROTROPIN SECRETION IN THE HYPOTHYROID RAT
Authors: Dou Yong‐Li , Tang Fai
Published: June 2007

1. Fourteen days after hypothyroidism was induced either by propylthiouracil (PTU) treatment or by thyroidectomy, the serum thyrotropin (TSH) responses to morphine (5 or 20 mg/kg bw), ether stress (30 min) and cold exposure (60 min) were compared with those in normal rats.

2. The decrease in serum TSH levels after morphine and ether stress found in the normal rats were abolished or much reduced respectively.

3. The increase in serum TSH in response to cold exposure and the diurnal rhythm of serum TSH (lower level at night) were also absent in the hypothyroid rat.

4. The stimulating effects of low dose of thyrotropin releasing hormone (TRH) and the inhibitory effects of somatostatin and apomorphine were completely abolished, while the stimulating effects of a high dose of TRH were much reduced in the hypothyroid rat.

5. These results indicate that in the hypothyroid rat the effect of a lack of negative feedback action of thyroid hormone predominates, and that hypothalamic factors are probably unimportant in the regulation of TSH secretion.
11β‐HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN MESENTERIC ARTERIES OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Takeda Yoshiyu , Yoneda Takashi , Miyamori Isamu , Gathiram Premjith , Takeda Ryoyu
Published: June 2007

1. 11β‐Hydroxysteroid dehydrogenase (11‐HSD) activity in mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats was determined and expressed as the percentage conversion of [3H]‐corticosterone to [3H]‐11‐dehydrocorticosterone.

2. 11‐HSD activity was significantly decreased in mesenteric arteries of both 4 and 9 week old SHR (8.4 ± 0.8%, 5.0 ± 1.5%, respectively) compared with WKY rats (12.4 ± 0.6%, 15.8 ± 0.7%, respectively; P≤ 0.05).

3. Total RNA from rat vascular smooth muscle cells (VSMC) and endothelial cells (EC) were prepared with selective precipitation in 3 mol/L LiC1/6 mol/L urea. The expression of 11‐HSD mRNA was confirmed in the rat VSMC but its mRNA expression was not detected in EC, using northern blot analysis.

4. The results in this study indicate that 11‐HSD in the vascular wall may play a role in the pathogenesis of hypertension in SHR.
SPECIES DIFFERENCES IN BINDING OF SUBMANDIBULAR NUCLEAR PROTEINS TO RENIN PROMOTER DNA
Authors: Loudon John A. , Fukamizu Akiyoshi , Murakami Kazuo , Morris Brian J.
Published: June 2007

1. Renin is highly expressed in submandibular gland (SMG) of mouse, which has two genes, Ren‐1d and Ren‐2d, but not at all in rat SMG. Differences in nuclear protein binding to renin promoter DNA were, therefore, explored.

2. Rat ‐169 to +23 renin DNA formed complexes with both mouse and rat extract, whereas a corresponding fragment of mouse Ren‐Id DNA (‐121 to +4) bound with rat extract, but much less so with mouse extract. Rat extract bound a ‐704 to ‐450 fragment of the Ren‐1d promoter. For Ren‐2d ‐578 to ‐383 and ‐786 to ‐718 DNA bound with mouse extract and ‐383 to +11 and ‐664 to ‐ 578 DNA bound with rat extract.

3. The results support a role for differences in presence or binding of species‐specific trans‐acting factors in the differential regulation of the renin gene in SMG of mouse and rat. Strong binding near the rat RNA polymerase II binding site could repress transcription in rat SMG, and binding peculiar to the Ret‐2d B2 element might contribute to high expression in mouse SMG.
RENAL SYMPATHETIC BAROREFLEX EFFECTS OF ANGIOTENSIN II INFUSIONS INTO THE ROSTRAL VENTROLATERAL MEDULLA OF THE RABBIT
Authors: Saigusa Takeshi , Head Geoffrey A.
Published: June 2007

1. The effects of local infusion of angiotensin II (AII) into the rostral ventrolateral medulla (RVLM) pressor area on the renal sympathetic baroreflex were compared with the excitatory amino acid glutamate in urethane anaesthetized rabbits with chronically implanted renal nerve electrodes. Baroreflex blood pressure‐renal nerve activity curves were obtained by intravenous infusion of phenylephrine and nitroprusside before and after treatments.

2. Infusion of 4 pmol/min of All into the RVLM increased blood pressure by 12 ± 2 mmHg and transiently increased resting sympathetic nerve activity. The renal sympathetic baroreflex curves were shifted to the right. The upper plateau of the sympathetic reflex increased by 29 ± 8% (n= 6, P < 0.025).

3. Infusions of glutamate into the RVLM, at a dose which was equipressor to that of AII, also increased resting renal sympathetic nerve activity. In contrast to AII, this increase was maintained throughout the infusion. Glutamate shifted the reflex curve to the right and increased the upper plateau of the sympathetic reflex by 44 ± 5% without affecting the lower plateau.

4. These results support the suggestion that AII can act at the level of the RVLM pressor area to facilitate baroreflex control of renal sympathetic activity in a similar fashion to that produced by fourth ventricular administration.

5. Thus the RVLM is a likely candidate site for modulation of the renal sympathetic baroreflex. The similarity of the actions of AII to those of glutamate suggest that it may directly excite sympathetic vasomotor cells in this region.
PROLIFERATIVE EFFECT OF MEVALONATE METABOLITES OTHER THAN ISOPRENOIDS ON CULTURED VASCULAR SMOOTH MUSCLE CELLS
Authors: Sawamura Makoto , Li Nanfan , Nara Yasuo , Yamori Yukio
Published: June 2007

1. Recent investigations revealed that isoprenoid compounds serve as key substances for cellular proliferation through post‐translational modification. Previously we reported that tissues of spontaneously hypertensive rats (SHR) had a lower activity of isoprenoid biosynthesis when compared with the normotensive control rat (WKY). However, cultured vascular smooth muscle cells (VSMC) of SHR showed an enhanced growth rate. These findings led us to investigate further the effect of isoprenoid compounds on VSMC proliferation.

2. When the cells of WKY were stimulated with 5% fetal calf serum (FCS) in the presence of lovastatin, [3H]‐thymidine incorporation decreased in a dose‐dependent manner and was completely inhibited at 30 μmol/L. Exogenously added mevalonate showed a protective effect against lovastatin (81% protection at 0.1 μmol/L).

3. Fluoromevalonate (Fmev), an inhibitor of mevalonate‐PP decarboxylase which converts mevalonate‐PP into isoprenoids, showed a dual inhibitory effect. DNA synthesis was partially inhibited at 0.01–1 μmol/L, however at 10 μmol/L there was no detectable inhibition. The inhibitory effect was again observed at concentrations over 10 μmol/L.

4. In the presence of lovastatin and Fmev to block both HMG CoA reductase and mevalonate‐PP decarboxylase, exogenous mevalonate dose dependently stimulated [3H]‐thymidine incorporation induced by FCS.

5. These data suggest the positive effect of the initial mevalonate derivatives other than isoprenoid compounds on the proliferation of VSMC.
EFFECT OF ATRIAL NATRIURETIC PEPTIDE ON CELLULAR ELEMENT CONCENTRATIONS IN RAT PROXIMAL TUBULES: EVIDENCE FOR INHIBITION OF THE SODIUM PUMP
Authors: Reddy Sri , Gyory Akos Z. , Dyne Marlen , Salipan‐Moore Noriah , Pollock Carol , Field Michael J. , Cockayne Dvid J. H.
Published: June 2007

1. In order to further define the action of atrial natriuretic peptide (ANP) on proximal tubular (PT) transport, combined clearance and electron microprobe X‐ray (EMPX) experiments were performed on five male Wistar rats infused with ANP (0.16 nmol/kg per h) and nine control animals.

2. Electron microprobe X‐ray analysis of PT cell electrolytes (mmol/ kg wet weight) revealed a similar [Na]i in both the control and ANP treated groups (16.4 ± 0.4 vs 16.5 ± 0.4; P= 0.894). [Cl]i was lower in the ANP treated animals (14.8 ± 0.3 vs 12.0 ± 0.3; P<0. 0001) as was [K]i (131.4 ± 1.4 vs 114 ± 1.7; P<0.0001). The PT cells in the ANP treated group had a significant reduction in dry weight (20.1 ± 0.3 g%vs 19.0 ± 0.3 g%; P<0.024), indicating significant cell swelling. Thus, despite a normal [Na]i, there was net accumulation of Nai following ANP treatment.

3. These results are consistent with accumulation of Nai due to inhibition of the Na pump followed by cell swelling and subsequent regulatory volume decrease with exit of K and Cl. These results are the first to show the effect of ANP on PT intracellular electrolytes.
CENTRAL NEURONS AND NEUROTRANSMITTERS IN THE CONTROL OF BLOOD PRESSURE
Authors: Chalmers John , Arnolda Leonard , Llewellyn‐Smith Ida , Minson Jane , Pilowsky Paul , Suzuki Satoshi
Published: June 2007

1. In this paper we review recent work from our laboratory on two major pathways important in the central control of blood pressure.

2. We report experiments on the sympatho‐excitatory bulbospinal pathway from the rostral ventral medulla. Here we focus particularly on the role of excitatory amino acids.

3. We review studies on the short inhibitory or depressor pathway ascending from the caudal to the rostral ventral medulla, which is thought to use γ‐aminobutyric acid (GABA) as its neurotransmitter. We report on experiments with the immediate early gene, c‐fos, demonstrating that its expression in the bulbospinal pressor neurons is increased by stimuli that activate these nerves, and that this expression can be blocked in vivo by treatment with an antisense oligonucleotide. We also show that basal and stimulated expression of the c‐fos gene is important in the central control of blood pressure.
EFFECTS OF ENALAPRIL AND DUP753 ON RENIN SYNTHESIS IN MICE WITH ONE HYDRONEPHROTIC KIDNEY
Authors: Zhang Yanling , Morgan Trefor
Published: June 2007

1. Renin synthesis and secretion were investigated in mice with one hydronephrotic kidney.

2. Enalapril and Dup753 stimulated renin synthesis to a similar extent in the hydronephrotic and normal kidney.

3. Hydronephrosis did not prevent an increase in renin mRNA caused by enalapril and Dup753.

4. The results therefore indicate that the macula densa does not appear to be crucial for renin synthesis in the kidney under the inhibition of angiotensin II.

5. Thus angiotensin II plays an important role controlling renin gene expression in both the normal and hydronephrotic kidneys.
INTRACEREBROVENTRICULAR ANP(1–28) HAS NO OBVIOUS EFFECTS ON RENAL BLOOD FLOW AND FUNCTION IN CONSCIOUS SHEEP
Authors: Gunnarsson U.
Published: June 2007

1. The study examines whether intracerebroventricular (ICV) infusion of atrial natriuretic peptide (human ANP, 1–28) influences renal electrolyte and water excretion, vasopressin release, renal and femoral blood flows in conscious ewes. The blood flow was measured by chronically implanted ultrasonic flow probes.

2. ICV infusion of ANP(1–28) at 25 pmol/min for 60 min did not affect renal Na and K excretion or plasma vasopressin levels. In two out of six animals a mild water diuresis developed at about 50 min post‐infusion.

3. The plasma osmolality, Na, K and protein concentrations did not change during the experiments.

4. The renal and femoral arterial blood flows were not influenced by 30 min ICV infusions of ANP(1–28) at 25 and 85 pmol/min.

5. It is concluded that human ANP(1–28) has no, or negligible, effects on renal function, femoral and renal blood flow when given ICV in amounts obviously elevating cerebrospinal fluid levels far above normal.
ROLE OF UTERINE FACTORS IN THE DEVELOPMENT OF HYPERTENSION IN SHR
Authors: Di Iulio Erkadius J. , Lucente F. , Bramich C. , Morgan T. , Nicolantonio R. Di
Published: June 2007

1. To examine whether the uterine environment plays a role in the development of hypertension in the spontaneously hypertensive rats (SHR), we have compared fetal weight, placental weight, and amniotic fluid composition of SHR and Wistar‐Kyoto (WKY) rats after 20 days of gestation.

2. Pregnant SHR and WKY were anaesthetized at 20 days of gestation and the uterus and embryonic sacs removed. Fetal and placental weights were recorded and amniotic fluid collected for measurement of volume, osmolality and electrolyte composition.

3. No significant difference was found in litter size and placental weight between SHR and WKY. Total embryonic sac weight and fetal weight of SHR were significantly lower than WKY. Amniotic fluid volume, sodium concentration and osmolality of SHR were significantly higher than WKY, while amniotic fluid potassium concentration of SHR was significantly lower than WKY.

4. Thus, the SHR foetus was significantly underweight compared to the WKY and was bathed in amniotic fluid with a significantly higher osmolality and sodium concentration. As the mature foetus is known to drink amniotic fluid, it is hypothesized that the elevated Na/K ratio in SHR amniotic fluid may instigate or accelerate the hypertensive process.
THE EFFECTS OF CENTRAL ADMINISTRATION OF ANGIOTENSIN II TYPE‐1 RECEPTOR ANTAGONIST, CV‐11974, IN NEPHRECTOMIZED SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Kamitani Atsushi , Higashimori Koichi , Kohara Katsuhiko , Higaki Jitsuo , Mikami Hiroshi , Ogihara Toshio
Published: June 2007

1. The role of the brain renin‐angiotensin system in the pathogenesis of genetic hypertension was evaluated using a specific non‐peptide angiotensin II type‐1 receptor antagonist, TCV‐116.

2. CV‐11974 (active metabolite of TCV‐116) was acutely injected either intravenously (i.v.) or intracerebroventricularly (i.c.v.) in male spontaneously hypertensive rats (SHR; 12 week old). In separate groups of nephrectomized and sham‐operated SHR, graded doses of CV‐11974 were administered either i.v. or i.c.v. for 2 days using an osmotic minipump. In another group, the effects of nephrectomy on the depressor effect of chronic treatment with CV‐11974 were investigated. Haemodynamics at three points: before infusion, before nephrectomy and 48 h after nephrectomy, were monitored.

3. Acute i.v. injection of CV‐11974 decreased blood pressure in the presence of the kidney. Prolonged i.c.v. administration of the drug for 2 days decreased blood pressure even at the lowest dosage, which had no hypotensive effects when given i.v. The hypotensive effect of centrally administered CV‐11974 was noted even 48 h after bilateral nephrectomy.

4. These results suggest that the brain renin‐angiotensin system has a primary role in the maintenance of hypertension after eliminating the circulating renin‐angiotensin system in SHR.
EFFECT OF NEUTRAL ENDOPEPTIDASE ON PLASMA AND TISSUE CONCENTRATIONS OF VASO‐ACTIVE INTESTINAL PEPTIDE
Authors: Duggan K. A. , Jones D. M. , Davis R. E. , Macdonald G. J.
Published: June 2007

1. This study sought to determine if neutral endopeptidase metabolizes vaso‐active intestinal peptide (VIP) and whether changes in the activity of this enzyme might explain the change in VIP metabolism which follows gastric sodium loading. The study also investigated whether prolonged inhibition of neutral endopeptidase was associated with inhibition of further secretion of VIP.

2. Male Sprague‐Dawley rats were given the neutral endopeptidase inhibitor UK77,568 (10 mg/kg), or vehicle, tail vein injected, once or daily for 4 days. Two hours after injection the rats were anaesthetized, blood sampled to determine plasma concentrations of VIP and the hearts were harvested. Plasma and tissue concentrations of VIP were determined by radio‐immunoassay.

3. Plasma VIP increased in response to UK77,568 at day 1 (P<0.0005) but did not differ from control at day 4. The concentration of VIP in the heart did not increase at day 1 but had increased significantly at day 4 (P<0.01).

4. It was concluded that neutral endopeptidase may metabolize VIP. Further, the increased concentration of VIP in the heart and the return of its plasma concentration to control levels at day 4 may be consistent with suppression of continued VIP secretion.
EFFECTS OF ENDOTHELIN‐1 ON ARTERIAL PRESSURE: A COMPARISON OF INTRAVENOUS AND INTRA‐ARTERIAL ADMINISTRATION IN CONSCIOUS RABBITS
Authors: Roberts‐Thomson P. , McRitchie R. J. , Cain M. D. , Chalmers J. P.
Published: June 2007

1. Intravenous endothelin‐1 releases endothelium‐derived relaxing factor (EDRF) and prostacyclin from the lungs, and substantial pulmonary clearance is claimed. Since these vaso‐active substances could alter the haemodynamic effects of endothelin‐1, the effects of boluses of endothelin‐1 injected intravenously and into the left ventricle (intra‐arterial) were compared, measuring arterial pressure and heart rate in conscious male New Zealand rabbits. The pulmonary clearance of endothelin‐1‐like immunoreactivity (Et‐1LI) and initial plasma half‐life were measured in anaesthetized rabbits during and after intravenous infusion of endothelin‐1.

2. The effects of intravenous and intra‐arterial routes of administration were not significantly different. Arterial pressure decreased (intravenous: 21.6, intra‐arterial: 24.2 mmHg, P= 0.12, n= 10, t‐test, 9 d.f.), then increased (intravenous: 21.2, intra‐arterial: 16.4 mmHg, P= 0.33), while heart rate increased (intravenous: 66, intra‐arterial: 53 beats/min, P = 0.09), then decreased (intravenous: 50, intra‐arterial: 54 beats/min, P= 0.30).

3. Arterial and venous plasma levels of Et‐1LI were not significantly different, venous levels increasing from 30 ± 3 pg/ mL (12 ± 1 pmol/ L) at 1 pmol/ kg per min to 770 ± 78 pg/ mL (308 ± 31 pmol/L) at 16 pmol/kg per min (n = 5). Mean initial plasma half‐life was 0.6 min (range: 0.25–1.1 min).

4. It was concluded that there is no significant net pulmonary clearance of exogenously administered endothelin‐1 in the conscious rabbit, and that any vaso‐active factors released in the lungs by endothelin‐1 do not have a significant effect on systemic arterial pressure.
INVOLVEMENT OF NITRIC OXIDE IN CORONARY VASCULAR RESPONSES TO 5‐HYDROXYTRYPTAMINE IN THE ANAESTHETIZED GREYHOUND
Authors: Woodman Owen L. , Dusting Gregory J.
Published: June 2007

1. The effect of the intracoronary (i.c.) injection of 5‐hydroxytryptamine (5‐HT; 0.1–1.0 μFg/ kg) was examined before and after inhibition of nitric oxide (NO) synthesis with N‐nitro‐l‐arginine (NOLA; 5 mg/ kg i.c.) in nine anaesthetized greyhounds. Before administration of NOLA, 5‐HT increased coronary blood flow (CBF) but decreased large coronary artery diameter indicating simultaneous dilatation of resistance vessels and constriction of large arteries.

2. The administration of NOLA significantly decreased large coronary artery diameter and increased systemic arterial pressure. There was no significant effect on coronary vascular resistance or heart rate. In the presence of NOLA, the 5‐HT‐induced constriction of the large coronary artery was enhanced and the dilatation of the resistance vessels was reduced. In addition there was a secondary reduction in CBF, a response that was not observed before NOLA treatment.

3. The response to NOLA suggests that a basal release of NO is important in the regulation of coronary and systemic vascular tone. Nitric oxide is an important mediator of coronary vasodilator responses to 5‐HT, and in addition the release of NO modulates 5HT‐induced constriction of large coronary arteries.
NEUROPEPTIDE Y IN CORTISOL‐INDUCED HYPERTENSION IN MALE VOLUNTEERS
Authors: Whitworth Judith A. , Williamson Paula M. , Brown Mark A. , Morris Margaret J.
Published: June 2007

1. Cortisol‐induced blood pressure rises in men are not accompanied by increases in plasma catecholamines. The present study examines the effects of cortisol on the sympathetic co‐transmitter, neuropeptide Y (NPY).

2. Eight normal men were given cortisol 200 mg/day over 5 days and haemodynamic, metabolic and hormonal measures were taken. Plasma NPY‐like immunoreactivity (NPY‐LI) concentrations were measured by direct radio‐immunoassay.

3. Cortisol significantly increased systolic, diastolic and mean arterial pressure, bodyweight, plasma glucose and total white cell concentration and decreased plasma potassium and total eosinophil count, as in previous studies. Plasma NPY concentrations were not altered significantly during cortisol treatment, but increased following cessation of cortisol treatment (P= 0.006).

4. The essentially unchanged pattern for NPY concentration with cortisol treatment resembles that previously reported for adrenaline and noradrenaline, but the increase in NPY on cortisol withdrawal was not seen for adrenaline or noradrenaline. These data do not support a role for sympathetic activation in the genesis of cortisol‐induced hypertension.
SEX DIFFERENCES IN THE PARASYMPATHETIC NERVE CONTROL OF RAT HEART
Authors: Du X‐J. , Dart A. M. , Riemersma R. A.
Published: June 2007

1. As it has been shown that oestrogen enhances the cholinergic muscarinic activity in the central nervous system, we studied sex differences in the responses to parasympathetic nervous stimulation in the rat heart using in vivo and in vitro preparations.

2. In in situ perfused, innervated hearts, stimulation of bilateral vagus nerves (15 Hz with 1 μmol/L physostigmine) inhibited sympathetic nerve stimulation (5 Hz) induced noradrenaline release to a greater extent in female than in male rats (54 ± 5 vs 72 ± 5% of control). Similarly, vagus nerve stimulation at 1–20 Hz reduced heart rate (HR) more in females than males, and this sex difference became more marked in the presence of physostigmine. The chronotropic effect of vagal stimulation was attenuated after ovariectomy but potentiated after castration when compared with sham‐operated controls. In contrast, the muscarinic agonist methacholine reduced neural NA release and HR equally well in both sexes.

3. In anaesthetized rats, reduction in HR and mean arterial pressure by vagus nerve stimulation (1–20 Hz) was more pronounced in females than in males after inhibition of acetylcholinesterase with physostigmine.

4. The results indicate that activation of parasympathetic nerve leads to greater presynaptic and postsynaptic effects in female than in male rat hearts, presumably due to a higher level of acetyl‐choline release following nerve activation.
THE EFFECT OF HIGH PERFUSION RATES ON THE ENDOTHELIAL DIFFUSION BARRIER IN RAT MESENTERIC ARTERIES IN VITRO
Authors: Lew Michael J. , Madeley Lisa J.
Published: June 2007

1. Arteries from Wistar‐Kyoto rat mesenteries were cannulated with glass cannulae and perfused with Krebs’ solution at controlled rates and distending pressure. Arterial diameter was measured and concentration—response curves generated with agonists applied via the perfusate (luminal) and via the solution bathing the outside of the preparation (extraluminal).

2. The α1‐adrenoceptor selective agonist methoxamine was about three times more potent when applied extraluminally than intraluminally in arteries perfused at either 25 or 500 μL/ min, but the lipophilic α1‐adrenoceptor selective agonist SKF 89748‐A was equally potent with either mode of application.

3. The extraluminal/intraluminal potency differentials for both methoxamine and noradrenaline were abolished by perfusion for 30 min at a rate calculated to give a high shear stress (100 dyn/cm2).

4. The potency of luminally applied acetylcholine was reduced less than two‐fold by the high shear perfusion, and the ability of acetylcholine to maximally relax the arteries was unchanged.

5. It is concluded that (i) the endothelium of small arteries reduces the potency of luminally applied lipophobic agonists by acting as a diffusion barrier; (ii) the ability of the endothelium to act as a diffusion barrier is easily damaged by shear stress in vitro; and (iii) the ability of acetylcholine to relax arteries in vitro is a poor index of the full functioning of the endothelium.
EFFECTS OF DILTIAZEM ON [3H]‐ACETYLCHOLINE RELEASE IN RAT CENTRAL NERVOUS SYSTEM
Authors: Tsuda Kazushi , Tsuda Seiko , Masuyama Yoshiaki , Goldstein Menek
Published: June 2007

1. In the present study, we examined the effects of a Ca2+ channel blocker, diltiazem, on [3H]‐acetylcholine (ACh) release in the rat CNS.

2. Diltiazem inhibited the electrically stimulated [3H]‐ACh release in a dose‐related fashion in striatal slices of Sprague‐Dawley (SD) rats. The basal release of [3H]‐ACh was not significantly affected by diltiazem except at a high concentration.

3. The stimulation‐evoked [3H]‐ACh release was not different between spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats.

4. The inhibitory effect of diltiazem on the stimulation‐evoked [3H]‐ACh release was significantly greater in SHR than in WKY rats.

5. The results show that diltiazem inhibited the stimulation‐evoked ACh release in the rat CNS. The pronounced effect of diltiazem in SHR suggests that the inhibition of central cholinergic activity might contribute, at least partially, to the hypotensive mechanisms of the Ca2+ channel blocker.
PRORENIN AND ACTIVE RENIN CONCENTRATIONS IN OVARIAN FOLLICULAR FLUID INCREASE AFTER THE LH PEAK IN SUPEROVULATED HEIFERS
Authors: Hagemann A. , Nielsen A. H. , Assey R. J. , Hyttel P. , Boland M. P. , Roche J. F. , Poulsen K.
Published: June 2007

1. The aim was to analyse the in vivo variations with time of prorenin and active renin and their relationship to steroid hormones in ovarian follicular fluid during follicular growth in heifers.

2. Thirty one beef heifers were assigned to two groups after oestrous synchronization: an unstimulated and a follicle‐stimulating hormone (FSH)‐treated (superovulated) group. Within each group, animals were slaughtered at different times of the follicular phase of the oestrous cycle. Ovarian follicular fluids were aspirated and analysed for the concentrations of active renin, prorenin, oestradiol‐17β (E2) and progesterone (P4).

3. Prorenin and active renin concentrations in follicular fluid remained constant until the luteinizing hormone (LH) peak, after which time they increased four‐ and two‐fold, respectively, in superovulated heifers.

4. In follicular fluid, prorenin and active renin correlated negatively with oestradiol and E2/P4 ratio but positively with progesterone during follicular growth in superovulated heifers. Prorenin also correlated negatively with oestradiol and E2/P4 ratio in unstimulated heifers.

5. The increase of renin concentrations in ovarian follicles after the LH peak and the correlations to steroid hormones suggest an important role of the ovarian renin‐angiotensin system in bovine follicular growth and maturation.
HYPERPROLIFERATION OF AORTIC SMOOTH MUSCLE CELLS AND FIBROBLASTS FROM YOUNG SHR RATS IS NOT SHARED BY ENDOTHELIAL CELLS
Authors: Battle Thierry , Arnal Jean‐François , Michel Jean‐Baptiste
Published: June 2007

1. To study the hypertensive genotypic influence on growth kinetics of the three aortic wall cell types.

2. Using young spontaneously hypertensive (SHR) and Wistar‐Kyoto (WKY) rats weighing 160–180 g, we compared the proliferative properties of endothelial cells (EC), smooth muscle cells (SMC) and fibroblasts that were isolated from the thoracic aorta of each strain and cultured. Growth‐arrested cells were exposed to P <‐thymidine after stimulation with 150 μg/mL endothelial cell growth supplement. Proliferation assays were performed by cell seeding on decellularized aortic explants and cell counting 2, 4, 5, 6 and 7 days after seeding. The influence of SMC from SHR on the growth kinetics of EC was evaluated by co‐cultures in transwell systems.

3. After stimulation, SMC from SHR exhibited a greater P <‐thymidine incorporation rate than those from WKY rats (ratios over controls: 3.90 ± 0.48 [7] vs 1.85 ± 0.25 [7] respectively, P < 0.05). This was also true for adventitial SHR fibroblasts: (13.1 ± 0.6 [6] vs 9.9 ± 1.0 [6] WKY P < 0.05). On the contrary, there was no difference in the P<‐thymidine incorporation rates between EC of each strain, regardless of the passage and the time considered. Cell proliferation on matrix explants confirmed the hyperproliferation of SMC and fibroblasts from SHR, while EC of each strain proliferated equally. Smooth muscle cells from SHR did not influence the growth kinetics of EC in co‐culture and vice versa.

4. The changes in growth patterns of aortic cells isolated from young prehypertensive SHR seem to be restricted to SMC and fibroblasts.
HEMATOLOGICAL ALTERATIONS AFTER ACUTE EXPOSURE TO HYPERBARIC OXYGEN IN RATS
Authors: Amin Hesham M. , Hakim Tawfic S. , Camporesi Enrico M.
Published: June 2007

1. Acute exposure to hyperbaric oxygen (HBO) is associated with a significant increase in haematocrit which returns to the control level after 24 h of recovery in room air. In this study we report changes in blood viscosity in Sprague‐Dawley rats after acute exposure to HBO.

2. The rats were divided into three groups: a control group included rats not exposed to HBO (CON), a group studied immediately after acute exposure to HBO at 283.7 kPa for 6 h (HBO), and a group allowed to recover for 24h in room air after HBO exposure (REC).

3. The viscosity of the whole blood, plasma and red blood cells (RBC) suspension was measured in the three groups. A significant increase in whole blood viscosity was detected in HBO and REC groups compared with CON (P<0.05), but no changes in the viscosity of the plasma or RBC suspension were noted.

4. A significant decrease in oxygen delivery index was found in the REC group compared with the CON and HBO groups (P<0.05).

5. In a subgroup of rats, several blood parameters known to influence blood viscosity were evaluated. A significant increase in plasma colloid oncotic pressure was noted in HBO rats compared with CON (P<0.01). A marked increase in platelet count and fibrinogen concentration was detected in HBO and REC rats compared with CON (P<0.05). Furthermore, a significant increase in total leukocytic count was noticed in REC group compared with CON and HBO (P<0.001).

6. We conclude that acute exposure to HBO induces a significant increase in whole blood viscosity which cannot be explained solely by the increase in haematocrit. Alterations in several blood components could lead to this phenomenon.
ω‐CONOTOXIN GVIA AND PRAZOSIN, BUT NOT FELODIPINE, CAUSE POSTURAL HYPOTENSION IN RABBITS
Authors: Hawkes Anna L. , Angus James A. , Wright Christine E.
Published: June 2007

1. The aim was to compare the effect of N‐type calcium channel blockade by ω‐conotoxin GVIA (ω‐CTX) with α1‐adrenoceptor or L‐type calcium channel blockade on postural adaptation in conscious rabbits.

2. Orthostatic responses were assessed by rapidly tilting the rabbits through 90° for 1 min. Tilts were performed before, 30 and 60 min after i.v. bolus administration of vehicle (propylene glycol 0.17mL/kg; n = 8), prazosin (0.5mg/kg; n= 8), felodipine (30μg/kg; n= 8) or ω‐CTX (3 & 7 μg/kg; n = 9).

3. Prazosin, felodipine or ω‐CTX caused significant falls in mean arterial pressure (MAP) with corresponding increases in heart rate (HR). Vehicle administration had no effect on MAP but caused a small fall in HR.

4. Before drug or vehicle administration, a small rise in MAP and HR occurred in response to tilt in all rabbits. In the vehicle treatment group, similar responses were observed to tilt at 30 and 60 min. Postural hypotension was observed in the prazosin treatment group, but not following administration of felodipine. Tilts 30 and 60 min after ω‐CTX (3μg/kg) caused an increase in HR but no change in MAP, different to the small pressor response observed following vehicle administration. However, following administration of ω‐CTX 7 μg/kg (total dose, 10μg/kg), significant falls in MAP with tachycardia were observed in response to tilt.

5. In conclusion, orthostatic hypotension was observed following acute αl‐adrenoceptor or N‐type calcium channel blockade in the conscious rabbit. These findings are compatible with the expectation that agents which are directly sympatholytic interfere with postural adaptation. In contrast, L‐type calcium channel antagonism with felodipine did not elicit postural hypotension.
HUMAN BUCCAL EPITHELIAL CELLS AS A POTENTIAL BIOCHEMICAL PREDICTOR OF ESSENTIAL HYPERTENSION: IDENTIFICATION OF KEY CELLULAR PROCESSES
Authors: McMurchie Edward J. , Head Richard J.
Published: June 2007

1. Human cheek cell Na+/H+ antiporter activity (measured as the rate of proton‐dependent 22Na+ uptake) was determined in seven normotensive (NT) and four hypertensive (HT) subjects following preincubation of cheek cells with a low molecular weight fraction isolated from NT saliva together with the ionophore, nigericin.

2. Cheek cells preincubated in this manner exhibited greater Na+/H+ antiporter activity with the mean values being 4.2 nmol Na+.mg protein. 5min for the NT group and 1.7 for the HT group.

3. It is possible that stimulation of Na+ transport is due to cellular accumulation of K+ ions during preincubation which, in the presence of the K+/H+ selective ionophore, nigericin, can cause cellular reacidification promoting further 22Na+ uptake via the Na+/H+ antiporter.