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Pontus B Persson

Publications and source records attributed to Pontus B Persson.

34 records · Page 2Linked to original sources
PubMed2003

Comparison of various techniques used to estimate spontaneous baroreflex sensitivity (the EuroBaVar study).

This study compared spontaneous baroreflex sensitivity (BRS) estimates obtained from an identical set of data by 11 European centers using different methods and procedures. Noninvasive blood pressure (BP) and ECG recordings were obtained in 21 subjects, including 2 subjects with established baroreflex failure. Twenty-one estimates of BRS were obtained by methods including the two main techniques of BRS estimates, i.e., the spectral analysis (11 procedures) and the sequence method (7 procedures) but also one trigonometric regressive spectral analysis method (TRS), one exogenous model with autoregressive input method (X-AR), and one Z method. With subjects in a supine position, BRS estimates obtained with calculations of alpha-coefficient or gain of the transfer function in both the low-frequency band or high-frequency band, TRS, and sequence methods gave strongly related results. Conversely, weighted gain, X-AR, and Z exhibited lower agreement with all the other techniques. In addition, the use of mean BP instead of systolic BP in the sequence method decreased the relationships with the other estimates. Some procedures were unable to provide results when BRS estimates were expected to be very low in data sets (in patients with established baroreflex failure). The failure to provide BRS values was due to setting of algorithmic parameters too strictly. The discrepancies between procedures show that the choice of parameters and data handling should be considered before BRS estimation. These data are available on the web site (http://www.cbi.polimi.it/glossary/eurobavar.html) to allow the comparison of new techniques with this set of results.

Adult↗
PubMed2003

Renin: origin, secretion and synthesis.

Renin is a central hormone in the control of blood pressure and various other physiological functions. In spite of the very early discovery of renin over 100 years ago, we have only recently gained a deeper understanding of the origin of renin-producing cells and of the mechanisms responsible for renin synthesis and secretion. The main source of renin is the juxtaglomerular cells (JGCs), which release renin from storage granules. Besides the renin-angiotensin system (RAS) in the JGCs, there exist local RASs in various tissues. JGCs originate in situ within the metanephric kidney from mesenchymal cells that are not related to smooth muscle lineages, as hitherto assumed. The previous notion that JGCs stem from vascular smooth muscle cells may be explained by JGC differentiation: they acquire smooth muscle markers that are maintained throughout adulthood. It has become clear that increasing intracellular free [Ca2+] inhibits renin secretion in JGCs. In contrast, cAMP stimulates renin release. Over the last decade, numerous studies on isolated JGCs and intact animals have provided contradictory results as to whether cGMP has a stimulatory or inhibitory action on renin release. More recent results strongly suggest that the effects of cGMP on renin release from JGCs involve the degradation of cAMP, which is modulated by cGMP. Finally, it has been found that not only is the production of renin modulated by enhancing or attenuating renin transcription, but renin mRNA stability is controlled by various proteins present in renin-producing cells.

Animals↗
PubMed2003

Posttranscriptional control of renin synthesis: identification of proteins interacting with renin mRNA 3'-untranslated region.

Stabilization and correct localization of mRNA are important features of renin synthesis. To elucidate the molecular basis of cAMP-mediated posttranscriptional control via mRNA stabilization, we analyzed the interaction of human preprorenin (hREN) mRNA 3'-untranslated region (3'-UTR) with proteins of renin synthesizing Calu-6 cells and investigated their functional impact on messenger integrity. To identify hREN mRNA binding proteins, electrophoretic mobility shift assays, UV cross-linking and RNA-affinity chromatography with subsequent matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were performed. The following six proteins were unambiguously identified as hREN mRNA 3'-UTR binding proteins: hnRNP E1 (synonyms alpha-CP or PCBP), hnRNP K, dynamin, nucleolin, YB-1, and MINT-homologous protein. All proteins contain various RNA binding motifs, and most have been described in the context of mRNA binding and mRNA stabilization. Four proteins for which antibodies were available were verified by immunological techniques (dynamin, nucleolin, hnRNP E1, and YB-1). Forskolin, an activator of cAMP synthesis, considerably stimulates renin synthesis via inhibition of REN mRNA decay. Functionally, this cAMP-based mRNA stabilization is accompanied by a 3- to 6-fold upregulation of REN mRNA binding proteins. RNase degradation assays confirm that 3'-UTR binding proteins are able to protect and stabilize REN mRNA in vitro.

3' Untranslated Regions↗
PubMed2003

Control of renin synthesis.

Studies published recently have considerably enhanced our understanding of the mechanisms controlling renin production. With regard to the control of renin transcription, two enhancer regions have been identified that markedly augment renin synthesis in cell lines. In the absence of this enhancer activity, the basic promoter of the renin gene increases transcription only two- to threefold. The location of one (Jones CA, Sigmund CD, McGowan RA, Kane-Haas CM, and Gross KW. Mol Endocrinol 4: 375-383, 1990) transcription enhancer in the mouse gene is at about -2.7 kb and in humans at roughly -11 kb. A second important region has been identified in a chorionic cell line to be located approximately 5 kb upstream of the transcription start site in humans. Another potentially important regulatory region may lie within approximately 3.9 kb upstream of the -11 kb enhancer, as suggested by several conserved sequences among species in this region. In addition to the control of renin transcription, it seems that renin translation and the stability of renin mRNA are also effectively regulated. This occurs via the 3'-untranslated region, to which several proteins can bind. The binding proteins were identified as hnRNP K and E1, dynamin, nucleolin, MINT homologous protein, and Y-Box 1.

Animals↗
PubMed2003

An evolutionary approach for identifying potential transcription factor binding sites: the renin gene as an example.

Evolutionary pressure has resulted in the conservation of certain nucleotide sequences. These conserved regions are potentially important for certain functions. Here we give an example of a comparison between noncoding sequences combined with other independent database information to shed light onto the regulation of the renin gene, a gene that has great importance for cardiovascular and renal homeostasis. To combine the information regarding conservation and weight matrices of transcription factor (TF) binding sites, an algorithm was developed (TFprofile). Notably, a local peak in the resulting binding profile coincides with a previously experimentally identified regulatory region for the renin gene. The existence of further peaks in the binding profile in the conserved 3.9-kb-long hRENc DNA block upstream of the renin gene suggests additional regions of potential importance for gene regulation. The algorithm TFprofile may be used to integrate information on cross-species evolutionary conservation and aspects of TF binding characteristics to provide putative regulatory DNA regions for experimental verification.

Animals↗
PubMed2003

Expression of smooth muscle MyHC B in blood vessels of hypertrophied heart in experimentally hypertensive rats.

We demonstrated recently a significantly lower fraction of cardiac precapillary arterioles that expressed smooth muscle myosin heavy chain (MyHC) B (SMB) in spontaneously hypertensive rats. To clarify whether this reduction of SMB expression is of genetic origin, we investigated SMB expression in cardiac precapillary arterioles of normotensive and experimentally hypertensive rats (one clip, one kidney or ANG II minipump). We observed similar SMB expression patterns in precapillary arterioles of experimentally hypertensive rats compared with normotensive controls. These observations suggest that the downregulation of SMB in spontaneously hypertensive rats is of genetic origin rather than an adaptive response to chronically enhanced blood pressure and cardiac hypertrophy.

Animals↗
PubMed2002

Renal blood flow autoregulation in blood pressure control.

Although the kidney strives to maintain its perfusion within tight boundaries, considerable blood flow fluctuations do occur. The reasons for this are the rather slow acting compensatory mechanisms of renal blood flow autoregulation, the effects of renal nerves, hormonal influences, etc. It seems that variations in renal perfusion can exert a major influence on renal excretory functions, on renin release and on blood pressure. The clinical importance of renal blood flow variability is not fully understood. In many situations, the absence of normal cardiovascular oscillations seems to be a risk factor. Large fluctuations in perfusion pressure to the kidney, however, in the long run, may induce target organ damage.

Animals↗
PubMed2001

Time-dependent autoregulation of renal blood flow in conscious rats.

Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow is mediated by a rapid myogenic response and a slower tubuloglomerular feedback mechanism. In 25 male conscious rats, ramp-shaped changes in RPP were induced to quantify dynamic properties of autoregulation. Decremental RPP ramps immediately followed by incremental ramps were made for four different rates of change, ranging from 0.118 to 1.056 mmHg/s. Renal blood flow and cortical and medullary fluxes were assessed, and the corresponding relative conductance values were calculated continuously. During RPP decrements, conductance increased. With increasing rate of change of RPP decrements, maximum conductance increased from 10% to 80%, as compared with control. This response, which indicates the magnitude of autoregulation, was more pronounced in cortical versus medullary vasculature. Pressure at maximum conductance decreased with increasing rate of change of RPP decrements from 88 to 72 mmHg. During RPP increments, dependence of maximum conductance changes on the rate of change was enhanced (-20 to 110% of control). Thus, a hysteresis-like asymmetry between RPP decrements and increments, a resetting of autoregulation, was observed, which in direction and magnitude depended on the rate of change and duration of RPP changes. In conclusion, renal vascular responses to changes in RPP are highly dependent on the dynamics of the error signal. Furthermore, the method presented allows differentiated stimulation of various static and dynamic components of pressure-flow relationship and, thus, a direct assessment of the magnitudes and operating pressure range of active mechanisms of pressure-flow relationships.

Animals↗
PubMed2001

Interaction of angiotensin II and nitric oxide in isolated perfused afferent arterioles of mice.

The present study was performed to evaluate angiotensin II (Ang II)-nitric oxide (NO) interaction in afferent arterioles (Af) of wild-type mice and mice that are homozygous (-/-) for disruption of the endothelial NO synthase (eNOS) gene. Af were microperfused, and the dose responses were assessed for the NO precursor L-arginine (n = 4), NO inhibitor NG-nitro-L-arginine methyl ester (L-NAME, n = 5), L-NAME after pretreatment with L-arginine (n = 5), Ang II (n = 8), and Ang II after pretreatment with L-NAME (n = 7). Acute administration of L-arginine and L-NAME (both in doses from 10(-6) to 10(-3) mol/L) did not change arteriolar diameter. Moreover, pretreatment with L-arginine did not change the response to L-NAME. However, Ang II, applied in doses of 10(-12), 10(-10), 10(-8), and 10(-6) mol/L, significantly reduced the lumen to 66.5 +/- 7.0% and 62.2 +/- 8.0% at 10(-8) and 10(-6) mol/L Ang II, respectively. The contraction was augmented after L-NAME pretreatment (19.5 +/- 13.6% and 25.5 +/- 10.2% at 10(-8) and 10(-6) mol/L Ang II, respectively). In eNOS (-/-) mice (n = 8), the response to Ang II also was enhanced (9.1 +/- 6.0% and 11.2 +/- 8.2% at 10(-8) and 10(-6) mol/L Ang II, respectively). Female mice did not differ from male mice in their reactivity to Ang II (n = 9) and Ang II + L-NAME pretreatment (n = 11). The study shows that (1) it is feasible to microperfuse mouse Af, (2) the basal production of endothelial NO is very low and not inducible by L-arginine in Af of mice, and (3) a counteracting effect of NO is initiated by Ang II. High Ang II sensitivity in eNOS (-/-) mice underscores the considerable role of endothelial-derived NO to balance Ang II vasoconstriction in Af.

Analysis of Variance↗
PubMed2001

Low-dose nitric oxide inhibition produces a negative sodium balance in conscious dogs.

Nitric oxide modulates renal hemodynamics and salt and water handling. Studies on the latter have provided conflicting results, however. Electrolyte and water balances were therefore studied in 28 beagles for 4 d, to determine the various effects of nitric oxide synthase (NOS) inhibition on renal function. The dogs were chronically equipped with aortic occluders to reduce renal perfusion pressure (RPP), bladder catheters, and catheters for measurements of RPP and mean arterial BP. A swivel system allowed free movement within the kennels. In a first set of experiments, a nonpressor dose of L-Nomega-nitroarginine (LN) (3 microg/min per kg body wt) was administered, to prevent increases in mean arterial BP and thus pressure effects on renin release and natriuresis. Remarkably, the nonpressor dose of LN caused a negative sodium balance. The natriuretic effect may involve reduced plasma renin activity, reduced aldosterone concentrations, and increased atrial natriuretic peptide concentrations. Changes in aldosterone levels, however, were the only parameters to parallel the time course of sodium excretion. In a second set of experiments, a sodium-retaining challenge was elicited by reduction of RPP. Dogs without NOS inhibition escaped sodium retention during RPP reduction after 2 d ("pressure escape"). LN neither ameliorated nor aggravated the sodium-retaining effect of reduced RPP, nor did it compromise the accomplishment of pressure escape. In conclusion, inhibition of NOS with a low dose of LN results in a reduction of total-body sodium. This effect mainly relies on reduced aldosterone concentrations. Furthermore, LN does not change the regulatory response to long-term RPP reduction.

Aldosterone↗
PubMed2000

Oxygen and renal hemodynamics in the conscious rat.

Previous studies have suggested a link between renal metabolism and local kidney hemodynamics to prevent potential hypoxic injury of particularly vulnerable nephron segments, such as the outer medullary region. The present study used three different inspiratory oxygen concentrations to modify renal metabolic state in the conscious rat (hypoxia 10% O2, normoxia 20% 02, and hyperoxia 100% 02). Renal blood flow (RBF) was assessed by ultrasound transit time; renal perfusion pressure (RPP) was controlled by a hydroelectric servo-control device. Local RBF was estimated by laser-Doppler flux for the cortical and outer medullary region (2 and 4 mm below renal surface, respectively). Hypoxia led to a generalized significant increase in RBF, whereas hyperoxia-induced changes did not (hypoxia 6.6 +/- 0.6 ml/min versus normoxia 5.7 +/- 0.7 ml/min, P < 0.05). Moreover, regional and total RBF autoregulation was markedly attenuated by hypoxia. Conversely, hyperoxia enhanced RBF autoregulation. Under normoxic and hyperoxic conditions, medullary RBF was very well maintained, even at low RPP (medullary RBF: approximately 70% of control at 50 mmHg). The hypoxic challenge, however, significantly diminished the capacity to maintain medullary blood flow at low RPP (medullary RBF: approximately 30% of control at 50 mmHg, P < 0.05). These data suggest that renal metabolism and renal hemodynamics are closely intertwined. In response to acute hypoperfusion, the kidney succeeds in maintaining remarkably high medullary blood flow. This is not accomplished, however, when a concomitant hypoxic challenge is superimposed on RPP reduction.

Animals↗
PubMedDate not supplied

The 'body fluid pressure control system' relies on the Renin-Angiotensin-aldosterone system: balance studies in freely moving dogs.

1. The physiological role of the 'renal body fluid pressure control system', including the intrarenal mechanism of 'pressure natriuresis', is uncertain. 2. Balance studies in freely moving dogs address the following questions: (i) what is the physiological contribution of pressure natriuresis to the control of total body sodium (TBS); (ii) to what extent is long-term mean arterial blood pressure (MABP) determined by TBS and total body water (TBW); and (iii) during Na accumulation, is Na stored in an osmotically inactive form? 3. Diurnal time-courses of Na excretion (U(Na)V) and MABP reveal no correlation. Spontaneous MABP changes do not affect U(Na)V. The long-term 20% reduction of renal perfusion pressure (RPP) results in Na retention via pressure-dependent stimulation of the renin-angiotensin-aldosterone system (RAAS), not via a pressure natriuresis mechanism. Prevention of pressure natriuresis does not result in ongoing Na retention when the RAAS is operative. The long-term 20% elevation of RPP induced by sustained TBS elevation facilitates Na excretion via pressure natriuresis, but does not restore TBS to normal. 4. Changes in TBW correlate well with changes in TBS (r(2) = 0.79). This correlation is even closer when concomitant changes in total body potassium are also considered (r(2) = 0.91). 5. With normal or elevated TBW, long-term MABP changes correlate well with TBW changes (r(2) = 0.69). At lowered TBW, no correlation is found. 6. In conclusion, the physiological role of pressure natriuresis is limited. Pressure natriuresis does not appear to be operative when RPP is changed from -20 to +10% and neurohumoral control of U(Na)V is unimpeded. Within this range, pressure-dependent changes in the RAAS mediate the effects of changes in RPP on U(Na)V. Pressure natriuresis may constitute a compensating mechanism under pathophysiological conditions of substantial elevation of RPP. A large portion of the long-term changes in MABP are attributable to changes in TBW. The notion of osmotically inactive Na storage during Na accumulation appears to be invalid.

Animals↗
PubMedDate not supplied

Angiotensin II-nitric oxide interaction in glomerular arterioles.

1. Resistance changes of the afferent and efferent arterioles determine blood flow and filtration rate in the kidney. The tone of both vessels results from the influence of nerves and humoral and paracrine factors, through a balance of constrictor and dilator systems. Angiotensin (Ang) II and nitric oxide (NO) are important factors determining vascular tone. 2. In the present review, we show that, in addition to the basal production of NO, a specific and significant AngII-induced release of NO occurs in glomerular arterioles. Data from investigations of arteriolar contraction, as well as from fluorescence measurements of NO, in the presence of selective angiotensin AT(1) and AT(2) receptor antagonists indicate an AT(1) receptor-stimulated release of NO in afferent arterioles. 3. The AngII-induced liberation of NO could prevent glomerular arterioles from a marked constriction, particularly in situations of high AngII levels in the kidney.

Angiotensin II↗