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G Lambert

Publications and source records attributed to G Lambert.

At least 55 records · Page 3Linked to original sources
PubMed2000

The functional unit of the renal type IIa Na+/Pi cotransporter is a monomer.

The composition of the functional unit of the rat renal type IIa Na(+)/P(i) cotransporter (NaPi-IIa) was investigated by using two approaches based on the differential sensitivities of the wild type (WT) and mutant S460C proteins to 2-aminoethylmethanethiosulfonate hydrobromide (MTSEA), a charged cysteine modifier. Transport activity of S460C is completely blocked after incubation in MTSEA, whereas that of the WT remains unaffected. First, Xenopus laevis oocytes were coinjected with cRNAs coding for the WT and S460C in different proportions, and the transport inhibition after MTSEA incubation was assayed by electrophysiology. The relationship between MTSEA inhibition and proportion of cRNA was consistent with that for a functional monomer. Second, concatameric proteins were constructed that either comprised two WT proteins (WT-WT), two S460C mutants (S460C-S460C), or one of each (WT-S460C). Western blots of oocytes injected with fusion protein cRNA showed bands at approximately 200 kDa, whereas a main band at approximately 90 kDa was obtained for the WT cRNA alone. The kinetic properties of concatamers were the same as for the single proteins. Transport activity of the WT-WT concatamer was unaffected by MTSEA incubation, fully inhibited for S460C-S460C, but 50% inhibited for WT-S460C. This behavior was also consistent with NaPi-IIa being a functional monomer.

Animals↗
PubMed2000

Cysteine residues and the structure of the rat renal proximal tubular type II sodium phosphate cotransporter (rat NaPi IIa).

The rat renal Na/P(i) cotransporter type IIa (rat NaP(i) IIa) is a 637 amino acid protein containing 12 cysteine residues. We examined the effect of different cysteine modifying methanethiosulfonate (MTS)-reagents and the disulfide bond reducing agent tris(2-carboxyethyl)phosphine (TCEP) on the transport activity of wild-type and 12 single cysteine substitution mutants of rat NaPi IIa expressed in Xenopus laevis oocytes. The transport activity of the wild-type protein was resistant to three membrane impermeant MTS-reagents (MTSEA, MTSET and MTSES). In contrast, membrane permeant methyl methanethiosulfonate (MMTS) and TCEP inhibited the transport activity of both the wild-type, as well as all the single mutant proteins. This indicated the existence of more than one functionally important cysteine residue, not accessible extracellularly, and at least 2 disulfide bridges. To identify the disulfide bridges, three double mutants lacking 2 of the 3 cysteine residues predicted to be extracellular in different combinations were examined. This led to the identification of one disulfide bridge between C306 and C334; reconsideration of the topological model predictions suggested a second disulfide bridge between C225 and C520. Evaluation of a fourth double mutant indicated that at least one of two disulfide bridges (C306 and C334; C225 and C520) has to be formed to allow the surface expression of a functional cotransporter. A revised secondary structure is proposed which includes two partially repeated motifs that are connected by disulfide bridges formed between cysteine pairs C306-C334 and C225-C520.

Amino Acid Sequence↗
PubMed2000

Cleavage of disulfide bonds leads to inactivation and degradation of the type IIa, but not type IIb sodium phosphate cotransporter expressed in Xenopus laevis oocytes.

Tris(2-carboxyethyl)phosphine (TCEP) reduces (cleaves) disulfide bonds of the renal proximal tubule type IIa Na/Pi- cotransporter (rat NaPi IIa) and thereby inhibits its function. We tested the effect of TCEP on the murine type IIa Na/P(i)-cotransporter and the corresponding IIb intestinal isoform both expressed in Xenopus laevis oocytes. After incubation with TCEP the function of NaPi IIa was inhibited and protein amount was decreased. Injection of the lysosomal inhibitor leupeptin prevented degradation of the protein. Exposure of oocytes to TCEP at 0 degrees C led to a reduction in transport function without concomitant loss in Na/Pi IIa protein. In contrast to NaPi type IIa, the type IIb isoform was neither inhibited, nor degraded after incubation with TCEP. These results suggest that cleavage of disulfide bonds led to changes within the confirmation of the type IIa transporter that result in (i) inhibition of the transport activity and (ii) internalization and subsequent lysosomal degradation of transporter protein. Sequence comparisons suggest the involvement/presence of different disulfide bonds in type IIa and type IIb Na/P(i)-cotransporters.

Amino Acid Sequence↗
PubMed2000

Disease progression and early viral dynamics in human immunodeficiency virus-infected children exposed to zidovudine during prenatal and perinatal periods.

Zidovudine (Zdv) is widely used to reduce maternal-infant human immunodeficiency virus transmission (HIV), but its consequences for disease progression among children infected despite Zdv exposure remain unknown. In a multicenter observational cohort study of 325 HIV-infected children born during 1986-1997, clinical progression was compared among infected children exposed or unexposed to Zdv during prenatal and perinatal periods. Zdv exposure was associated with 1.8-fold (95% confidence interval, 1.02-3.11) increased risk of progressing to AIDS or death after adjusting for year of birth, maternal CD4 cell count, maternal AIDS diagnosis, and subsequent antiretroviral therapy of the child. Mean log(10) viral copies at 7-12 weeks were higher among Zdv-exposed children (P=.004). No infected child treated early with multidrug therapy progressed to AIDS or died by 1 year, regardless of early Zdv exposure. More rapid disease progression was observed among infected children exposed during pregnancy or birth to Zdv if effective multidrug therapy was not initiated.

Anti-HIV Agents↗
PubMed2000

Endogenous renin and related short-term blood pressure variability in the conscious rat.

This study was designed to investigate, by use of spectral analysis, the blood pressure variability changes induced in the conscious rat by activation of plasmatic renin activity. Rats were surgically prepared with a supra-renal catheter inserted via the left carotid artery to perform the infusions, and with a femoral artery catheter to measure blood pressure and heart rate. Secretion of renin was induced using beta-adrenoceptor stimulation produced by isoprenaline. A first group (n=8) was infused with isoprenaline: 0.003, 10, 100 and 300 ng/kg/min, at a rate of 20 microl/min. A second group (n=8) was given a bolus injection of the angiotensin AT(1) receptor antagonist, valsartan (2 mg/kg, i.a.), prior to isoprenaline infusions. The lack of effect of infusion per se was checked in additional animals (n=8) infused with saline only (20 microl/min). Five other groups of animals were prepared with arterial catheters as mentioned previously. Each group received one concentration of infused isoprenaline and samples of blood were collected for further determinations of plasma renin activity and catecholamine concentrations. Blood pressure recordings were analysed using the fast Fourier transform on 2048 points time series (204.8 s). Isoprenaline increased plasma renin activity and did not modify plasma catecholamine concentrations. The low-frequency (0.02-0.2 Hz) component of the systolic blood pressure variability was amplified by isoprenaline (10 ng/kg/min isoprenaline: 4.16+/-0.62 mm Hg(2) vs. 2.90+/-0.44 mm Hg(2) for control value, P<0.05), a concentration that did not alter either blood pressure or heart rate levels. Isoprenaline lowered blood pressure and increased heart rate, starting at concentrations of 100 ng/kg/min. Valsartan, whose principal effect was generation of tachycardia (+25 bpm) modified neither blood pressure levels nor blood pressure variability. Valsartan prevented the amplification of the low-frequency oscillations of systolic blood pressure induced by isoprenaline (10 ng/kg/min isoprenaline: 2.53+/-0.38 mm Hg(2) vs. 2.20+/-0.25 mm Hg(2) for control value (valsartan, ns). We conclude that a moderate increase of plasma renin activity enhanced systolic blood pressure variability in the low-frequency range, without affecting blood pressure and heart rate levels.

Adrenergic beta-Agonists↗
PubMed2000

Molecular determinants of pH sensitivity of the type IIa Na/P(i) cotransporter.

Type II Na/P(i) cotransporters play key roles in epithelial P(i) transport and thereby contribute to overall P(i) homeostasis. Renal proximal tubular brush border membrane expresses the IIa isoform, whereas the IIb isoform is preferentially expressed in small intestinal brush border membrane of mammals. IIa and IIb proteins are predicted to contain eight transmembrane domains with the N- and C-terminal tails facing the cytoplasm. They differ in their pH dependences: the activity of IIa increases at higher pH, whereas the IIb shows no or a slightly opposite pH dependence. To determine the structural domains responsible for the difference in pH sensitivity, mouse IIa and IIb chimeras were constructed, and their pH dependence was characterized. A region between the fourth and fifth transmembrane domains was required for conferring pH sensitivity to the IIa-mediated Na/P(i) cotransport. Sequence comparison (IIa versus IIb) of the third extracellular loops revealed a stretch of three charged amino acids in IIa (REK) replaced by uncharged residues in IIb (GNT). Introduction of the uncharged GNT sequence (by REK) in IIa abolished its pH dependence, whereas introduction of the charged REK stretch in IIb (by GNT) led to a pH dependence similar to IIa. These findings suggest that charged residues within the third extracellular loop are involved in the pH sensitivity of IIa Na/P(i) cotransporter.

Amino Acid Sequence↗
PubMed2000

Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders.

BACKGROUND: The etiology of depressive illness has been linked with brain monoaminergic neuronal dysfunction, yet the development of sensitive markers of endogenous depression has proven difficult. METHODS: Using catheters placed in an internal jugular vein, we estimated the release of brain monoamine neurotransmitters in 19 healthy volunteers and in 9 patients with nonbipolar depressive illness refractory to medication at rest and following intravenous desipramine hydrochloride. Venoarterial plasma concentration gradients were used to quantify the amount of neurotransmitters stemming from the brain. Cerebral oxidative metabolism was assessed concurrently from measurements of oxygen and carbon dioxide gas exchange via the process of regional indirect calorimetry. RESULTS: The brains of these patients exhibited reduced venoarterial norepinephrine (4.0 +/- 2.7 nmol/L vs 0.7 +/- 1.3 nmol/L) and homovanillic acid concentration gradients (8.3 +/- 7.8 nmol/L vs 3.1 +/- 1.9 nmol/L), and used an energy source other than glucose. Internal jugular 5-hydroxyindoleacetic acid concentration gradients were not reduced in the patients with depressive illness. While both the reduction in norepinephrine turnover and the defect in cerebral metabolism were normalized following pharmacological blockade of the norepinephrine transporter with desipramine, paradoxically it was the brain's turnover of dopamine that bore a significant relation to the patients' clinical status (r(s) = 0.79, P =.02). The positive nature of this relationship remains difficult to reconcile. CONCLUSIONS: In accordance with the monoamine hypothesis, a deficit in brain norepinephrine and dopamine exists in patients with depressive illness. Moreover, the brains of these patients use an energy source other than glucose, a situation that is normalized following the acute pharmacological blockade of the norepinephrine transporter with the tricyclic antidepressant, desipramine.

Adult↗
PubMed2000

Subarachnoid hemorrhage induced sympathoexcitation arises due to changes in endothelin and/or nitric oxide activity.

OBJECTIVE: The demonstration of the effectiveness of endothelin antagonists and nitric oxide donors in managing vasospasm following subarachnoid hemorrhage is encouraging. Whether such drugs can modify the sympathoexcitation that accompanies this condition remains unknown and was the basis for the present report. METHODS: Subarachnoid hemorrhage was induced in conscious rats by injecting blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. We combined measurements of arterial plasma catecholamines with the spectral analysis of blood pressure variability in order to examine sympathetic nervous activation following subarachnoid hemorrhage. Experiments were performed in untreated animals and in rats following pretreatment with either bosentan or sodium nitroprusside. RESULTS: Indicative of a pronounced sympathoexcitation, the 0.2-0.6 Hz frequency components of blood pressure were markedly elevated following subarachnoid hemorrhage (2.5 +/- 0.5 vs. 8.9 +/- 2.6 mmHg2, P < 0.01). Parallel changes in plasma norepinephrine concentration were observed (1.0 +/- 0.2 vs. 2.4 +/- 0.4 nmol/l, P < 0.01). The subarachnoid injection of saline did not modify blood pressure variability or plasma norepinephrine concentrations. Pretreatment with either bosentan or sodium nitroprusside completely prevented the subarachnoid hemorrhage induced sympathoexcitation. CONCLUSIONS: Experimental subarachnoid hemorrhage is associated with a pronounced activation of the sympathetic nervous system. It would appear that this sympathoexcitation has its roots ensconced in either the release of endothelin or an impairment in nitric oxide mediated vasodilation.

Animals↗
PubMed2000

Biotransformation of trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene to benzo[a]pyrene bis-diols and DNA adducts by induced rat liver microsomes.

The biotransformation of (+/-)-trans-4,5-dihydroxy-4, 5-dihydrobenzo[a]pyrene (trans-B[a]P-4,5-diol), the K-region dihydrodiol of B[a]P, by beta-naphthoflavone (BNF)-induced rat liver microsomes was studied. trans-B[a]P-4,5-diol was metabolized to six major products as characterized by NMR, MS, and UV spectroscopy, and all were identified as bis-diols: two diastereomers of trans,trans-4, 5:7,8-tetrahydroxy-4,5:7,8-tetrahydrobenzo[a]pyrene (trans, trans-B[a]P-4,5:7,8-bis-diol), two diastereomers of trans,trans-4, 5:9,10-tetrahydroxy-4,5:9,10-tetrahydrobenzo[a]pyrene (trans, trans-B[a]P-4,5:9,10-bis-diol), and two diastereomers of the somewhat unusual trans,trans-1,2:4,5-tetrahydroxy-1,2:4, 5-tetrahydrobenzo[a]pyrene (trans,trans-B[a]P-1,2:4,5-bis-diol). BNF-induced rat liver microsomes also metabolized B[a]P to the same trans-B[a]P-4,5-diol-derived bis-diols. The ability of trans-B[a]P-4, 5-diol to form DNA adducts was investigated using (32)P-postlabeling techniques specifically designed to detect stable polar DNA adducts. Four DNA adducts were detected after microsomal activation of trans-B[a]P-4,5-diol with calf thymus DNA. Further analyses indicated that each of these stable polar DNA adducts was derived from the further metabolic activation of the trans,trans-B[a]P-4,5:7, 8-bis-diols. We conclude that trans-B[a]P-4,5-diol can be metabolized to a series of B[a]P-bis-diols, and can also be metabolically activated to form stable polar DNA adducts. The trans, trans-B[a]P-4,5:7,8-bis-diols were shown to be metabolic intermediates in the formation of these DNA adducts.

Animals↗
PubMed2000

Polyisobutylcyanoacrylate nanocapsules containing an aqueous core as a novel colloidal carrier for the delivery of oligonucleotides.

PURPOSE: The goal of the present paper was to encapsulate oligonucleotides in a new particulate carrier in order to protect them from enzymatic degradation. METHODS: Nanocapsules with an aqueous core containing oligonucleotides were prepared by interfacial polymerization of isobutylcyanoacrylate in a W/O emulsion. Ultracentrifugation and re-suspension in water yielded a dispersion of these containing an aqueous core nanocapsules. Zeta potential measurements and quenching of fluorescence of fluorescein-bounded oligonucleotides were used to study the localization of the oligonucleotides. Oligonucleotide degradation studies were carried out in fetal calf serum. RESULTS: Polydisperse nanocapsules of size ranging from 20 to 400 nm were obtained. Oligonucleotide loading did not significantly influence the zeta potential, suggesting they were located within the core of the nanocapsules. Fluorescence quenching assays confirmed this localization. When encapsulated in the nanocapsules and incubated in the presence of serum, the oligonucleotides were efficiently protected from degradation by nucleases, whereas oligonucleotides adsorbed onto nanospheres were protected less efficiently. CONCLUSIONS: This paper describes, for the first time, a nanotechnology able to encapsulate oligonucleotides rather than adsorbing them at the surface of a solid support. Such a formulation has great potential for oligonucleotide delivery.

Colloids↗
PubMed2000

Tuberculosis in human immunodeficiency virus-infected and human immunodeficiency virus-exposed children in New York City. The New York City Pediatric Spectrum of HIV Disease Consortium.

BACKGROUND: Tuberculosis disease incidence increased sharply in New York City (NYC) in the late 1980s in children and adults. The relationship of tuberculosis disease in adults with the coincident epidemic of immunosuppression caused by HIV disease has been well-documented. This paper examines the relationship of tuberculosis and HIV in children in NYC. METHODS: Information on tuberculosis was collected by retrospective chart abstraction in a cohort of HIV-exposed and infected children enrolled in a longitudinal study of HIV. Tuberculosis cases were ascertained by chart review or by matching HIV-infected and -exposed children to NYC Tuberculosis Registry cases. NYC Tuberculosis Registry data on children reported from 1989 to 1995, and not reported as HIV-infected, were used for comparison. RESULTS: Tuberculosis disease was found in 45 (3%) of 1426 HIV-infected children (0.61 per 100 child years of observation) and in 5 (0.5%) of 1085 HIV-exposed uninfected children (0.2 per 100 child years). 30% of children were evaluated for HIV only after presenting with tuberculosis. Children with tuberculosis and HIV were more likely than other age-matched HIV-infected children to have decreased CD4+ T lymphocyte counts (66% vs. 37%, P = 0.02) and more likely than other NYC children with tuberculosis to have culture-confirmed and extrapulmonary tuberculosis. In this series 8 of 21 deaths in HIV-infected children with tuberculosis appeared to be related to tuberculosis. CONCLUSIONS: During a period of high tuberculosis incidence in NYC, 3% of HIV-infected children in our cohort had tuberculosis, higher than the rate in uninfected children born to HIV-positive mothers in the same cohort. Because of this association, HIV-infected children with pulmonary illness should be tested for tuberculosis; and all children with tuberculosis should be tested for HIV.

AIDS-Related Opportunistic Infections↗
PubMed2000

Lecithin-cholesterol acyltransferase: role in lipoprotein metabolism, reverse cholesterol transport and atherosclerosis.

In the past several years significant advances have been made in our understanding of lecithin-cholesterol acyltransferase (LCAT) function. LCAT beneficially alters the plasma concentrations of apolipoprotein B-containing lipoproteins, as well as HDL. In addition, its proposed role in facilitating reverse cholesterol transport and modulating atherosclerosis has been demonstrated in vivo. Analysis of LCAT transgenic animals has established the importance of evaluating HDL function, as well as HDL plasma levels, to predict atherogenic risk.

Animals↗
PubMed2000

Characterization of the operon encoding the alternative sigma(B) factor from Bacillus anthracis and its role in virulence.

The operon encoding the general stress transcription factor sigma(B) and two proteins of its regulatory network, RsbV and RsbW, was cloned from the gram-positive bacterium Bacillus anthracis by PCR amplification of chromosomal DNA with degenerate primers, by inverse PCR, and by direct cloning. The gene cluster was very similar to the Bacillus subtilis sigB operon both in the primary sequences of the gene products and in the order of its three genes. However, the deduced products of sequences upstream and downstream from this operon showed no similarity to other proteins encoded by the B. subtilis sigB operon. Therefore, the B. anthracis sigB operon contains three genes rather than eight as in B. subtilis. The B. anthracis operon is preceded by a sigma(B)-like promoter sequence, the expression of which depends on an intact sigma(B) transcription factor in B. subtilis. It is followed by another open reading frame that is also preceded by a promoter sequence similarly dependent on B. subtilis sigma(B). We found that in B. anthracis, both these promoters were induced during the stationary phase and induction required an intact sigB gene. The sigB operon was induced by heat shock. Mutants from which sigB was deleted were constructed in a toxinogenic and a plasmidless strain. These mutants differed from the parental strains in terms of morphology. The toxinogenic sigB mutant strain was also less virulent than the parental strain in the mouse model. B. anthracis sigma(B) may therefore be a minor virulence factor.

Animals↗
PubMed2000

Increased sympathetic nervous activity in patients with nontraumatic subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Activation of the sympathetic nervous system, which leads to elevation of circulating catecholamines, is implicated in the genesis of cerebral vasospasm and cardiac aberrations after subarachnoid hemorrhage. To this juncture, sympathetic nervous testing has relied on indirect methods only. METHODS: We used an isotope dilution technique to estimate the magnitude and time course of sympathoadrenal activation in 18 subarachnoid patients. RESULTS: Compared with 2 different control groups, the patients with subarachnoid hemorrhage exhibited an approximately 3-fold increase in total-body norepinephrine spillover into plasma within 48 hours after insult (3.2+/-0.3 and 4.2+/-0.7 versus 10.2+/-1.4 nmol/L; P<0.05 versus both). This sympathetic activation persisted throughout the 7- to 10-day examination period and was normalized at the 6-month follow-up visit. CONCLUSIONS: The present study has established that massive sympathetic nervous activation occurs in patients after subarachnoid hemorrhage. This overactivation may relate to the well-known cardiac complications described in subarachnoid hemorrhage.

Adult↗
PubMed2000

Housing needs of consumers of mental health services in rural New South Wales, Australia.

A survey of the housing needs of 101 people with mentally illness treated by the Central Western Area Mental Health Service were compared with data from the 1994 Australian Housing Study (Australian Bureau of Statistics). The results indicate that people with mental illness want housing similar to Australians in general. However, unemployment or very low incomes may affect their ability to realise their housing choices. Despite very low incomes most in the survey felt their rent was affordable. Preferences for housing types and factors relating to housing choice are described. The results are discussed in relation to the importance of housing in maintaining mental health.

Adult↗
PubMed2000

Hepatic lipase deficiency decreases the selective uptake of HDL-cholesteryl esters in vivo.

Recent in vitro studies have provided evidence that hepatic lipase (HL) facilitates the selective uptake of HDL cholesteryl esters (CE), but the in vivo physiological relevance of this process has not been demonstrated. To evaluate the role that HL plays in facilitating the selective uptake of HDL-CE in vivo, we studied the metabolism of [(3)H]CEt, (125)I-labeled apolipoprotein (apo) A-I, and (131)I-labeled apoA-II-labeled HDL in HL-deficient mice. Kinetic analysis revealed similar catabolism of (125)I-labeled apoA-I (as well as (131)I-labeled apoA-II) in C57BL controls and HL deficient mice, with fractional catabolic rates (FCR) of 2.17 +/- 0.15 and 2.16 +/- 0.11 d(-)(1) (2.59 +/- 0.14 and 2.67 +/- 0.13 d(-)(1), respectively). In contrast, despite similar hepatic scavenger receptor BI expression, HL-deficient mice had delayed clearance of [(3)H]CEt compared to controls (FCR = 3.66 +/- 0.29 and 4.41 +/- 0.18 d(-)(1), P < 0.05). The hepatic accumulation of [(3)H]CEt in HL-deficient mice (62.3 +/- 2.1% of total) was significantly less than in controls (72.7 +/- 3.0%), while the [(3)H]CEt remaining in the plasma compartment increased (20.7 +/- 1.8% and 12.6 +/- 0.5%) (P < 0.05, all). In summary, HL deficiency does not alter the catabolism of apoA-I and apoA-II but decreases the hepatic uptake and the plasma clearance of HDL-CE. These data establish for the first time an important role for HL in facilitating the selective uptake of HDL-CE in vivo.

Animals↗
PubMed2000

[Activation of the renin-angiotensin system and blood pressure variability in rats].

This study was designed to assay, using spectral analysis, the influence of the renin-angiotensin system activation on the blood pressure variability. Rats were surgically prepared with a supra-renal catheter inserted via the left carotid artery to perform local infusions and with a femoral artery catheter to measure blood pressure (BP) and heart rate (HR). The beta-adrenoceptors stimulation by isoprenaline was used to increase the plasma renin activity (PRA). A first group (n = 8) was infused with isoprenaline (0, 0.003, 10, 100, 300 ng/kg/min) at a rate of 20 microL/min. A second group (n = 8) received a bolus of the angiotensin II (AII) AT1 receptor-antagonist valsartan (2 mg/kg/mL, i.a.) prior to isoprenaline infusions. Five groups were used for blood sampling (one group infused with one concentration of isoprenaline) to assay PRA and catecholamines (CA). BP recordings were analysed using the fast Fourier transforms (FFT) on 2048 points time series (204.8 s). Isoprenaline from the concentration of 10 ng/kg/min increased PRA with a maximum effect of 8.5 fold with the highest concentration (300 ng/kg/min, p < 0.05); CA were not modified. Isoprenaline amplified the low-frequency (LF: 0.02-0.20 Hz) component of the systolic BP (SBP) variability (10 ng/kg/min: 4.16 +/- 0.62 mmHg2 versus: 2.90 +/- 0.44 mmHg2 for control value, p < 0.05) even if it did not modify BP and HR levels. Isoprenaline lowered BP and had a tachycardic effect at concentrations > or = 100 ng/kg/mL (at 100 ng/kg/mL: SBP = 115 +/- 3 mmHg, HR = 464 +/- 15 bpm, versus control: SBP = 128 +/- 3 mmHg, HR = 351 +/- 7 bpm, p < 0.05). Valsartan modified neither BP levels nor BP variability but exerted a tachycardic effect (+25 bpm, p < 0.001). Valsartan prevented the amplification of the LF oscillations of SBP induced by isoprenaline (10 ng/kg/min: 2.53 +/- 0.38 mmHg2 versus: 2.20 +/- 0.25 mmHg2 for control value (valsartan), ns). We conclude that a moderate endogenous production of renin increases SBP variability in the LF range in the conscious rat. This effect which does not affect BP and HR levels is mediated by AII AT1 receptors and does not involve the sympathetic nervous system.

Adrenergic beta-Agonists↗