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H Ehmke

Publications and source records attributed to H Ehmke.

At least 37 records · Page 2Linked to original sources
PubMed1999

Interaction between nitric oxide and endogenous vasoconstrictors in control of renal blood flow.

The level of renal blood flow (RBF) is controlled by opposing vasoconstrictor and vasodilator influences. In a recent investigation in normotensive dogs, we found that combined blockade of endothelin type A (ET(A)) receptors and angiotensin II formation induces marked increases in RBF that were much larger than the effects of blocking either system alone. The aim of the present study was to determine the contribution of nitric oxide (NO) to this vasodilator response. Experiments were made in 6 conscious, chronically instrumented dogs subjected to 5 different experimental treatments on separate days. Blockade of ET(A) receptors alone by the selective antagonist LU 135252 had only minor effects on RBF compared with time-control experiments. Additional blockade of angiotensin II formation by angiotensin-converting enzyme inhibition with trandolaprilat caused a substantial increase of RBF by approximately 50%. This vasodilation was entirely suppressed when NO formation was prevented by inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester HCl. However, when during NO synthase inhibition renal vascular NO concentrations were clamped at control levels by infusing the NO donor S-nitroso-N-acetyl-D, L-penicillamine, the vasodilator response to combined blockade of ET(A) receptors and angiotensin II formation was completely restored (DeltaRBF approximately 60%). These results indicate that the vasodilation after combined ET(A) receptor blockade and angiotensin-converting enzyme inhibition is not mediated by an increase in NO release but results from the unmasking of the tonic influence that is normally exerted by constitutively released NO. Accordingly, the tonic activity of endothelial NO synthase appears to be of major importance in the physiological regulation of renal vascular resistance by determining the vasomotor responses to endothelin and angiotensin II.

Angiotensin II↗
PubMed1998

Buffering of blood pressure variability by the renin-angiotensin system in the conscious dog.

1. The renin-angiotensin system (RAS) participates in the compensation of major blood pressure disturbances such as haemorrhage and is involved in the tonic long-term (> 1 day) maintenance of mean arterial blood pressure (MABP). Since its contribution to the short-term (< 1 h) buffering of normal blood pressure variability is not known, this was investigated in resting conscious dogs. 2. The regulatory efficiency and the response time of the RAS were studied by an acute step reduction of renal artery pressure to 70 mmHg for 1 h using a suprarenal aortic cuff. After a delay of at least 100 s, MABP rose exponentially by 22 +/- 5 mmHg in normal dogs (n = 4), by 6 +/- 3 mmHg after angiotensin converting enzyme (ACE) inhibition (n = 4), and by 25 +/- 5 mmHg after ganglionic blockade (n = 4). MABP returned to control after release of the cuff with similar time courses. The time constants of the MABP responses were in the range of 20 min. Thus, possible feedback oscillations of the RAS would be expected around 0.0025 Hz (1/(4 x 100 s)); a buffering effect would be possible below this frequency. 3. Blood pressure variability was investigated by spectral analysis of MABP from 3.75 h recordings in the frequency ranges of 0.002-0.003 Hz (feedback oscillations) and below 0.002 Hz (buffering effect). 4. ACE inhibition (n = 7) decreased MABP by 11 +/- 2 mmHg (P < 0.05), but in both frequency ranges integrated spectral density was not affected. ACE inhibition also failed to significantly change spectral density in either of the two frequency ranges under the following conditions: (1) during ganglionic blockade (n = 7), (2) during a low-sodium diet (except for a very slight elevation below 0.002 Hz) (n = 7), and (3) when the fall of MABP induced by ACE inhibition was compensated by an angiotensin II infusion (n = 7). 5. It is concluded that in spite of its high regulatory efficiency with an adequate response time the RAS does not directly contribute to the short-term buffering of blood pressure variability, nor does it give rise to feedback oscillations under normal resting conditions. Even if the RAS is stimulated by sodium restriction its contribution to short-term blood pressure buffering is only marginal.

Angiotensin II↗
PubMed1998

Functional and molecular differences between voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus.

We have examined gating and pharmacological characteristics of somatic K+ channels in fast-spiking interneurons and regularly spiking principal neurons of hippocampal slices. In nucleated patches isolated from basket cells of the dentate gyrus, a fast delayed rectifier K+ current component that was highly sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (half-maximal inhibitory concentrations <0.1 mM) predominated, contributing an average of 58% to the total K+ current in these cells. By contrast, in pyramidal neurons of the CA1 region a rapidly inactivating A-type K+ current component that was TEA-resistant prevailed, contributing 61% to the total K+ current. Both types of neurons also showed small amounts of the K+ current component mainly found in the other type of neuron and, in addition, a slow delayed rectifier K+ current component with intermediate properties (slow inactivation, intermediate sensitivity to TEA). Single-cell RT-PCR analysis of mRNA revealed that Kv3 (Kv3.1, Kv3.2) subunit transcripts were expressed in almost all (89%) of the interneurons but only in 17% of the pyramidal neurons. In contrast, Kv4 (Kv4.2, Kv4.3) subunit mRNAs were present in 87% of pyramidal neurons but only in 55% of interneurons. Selective block of fast delayed rectifier K+ channels, presumably assembled from Kv3 subunits, by 4-AP reduced substantially the action potential frequency in interneurons. These results indicate that the differential expression of Kv3 and Kv4 subunits shapes the action potential phenotypes of principal neurons and interneurons in the cortex.

4-Aminopyridine↗
PubMed1998

Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice.

Fibroblast growth factor-2 (FGF-2) has been implicated in various signaling processes which control embryonic growth and differentiation, adult physiology and pathology. To analyze the in vivo functions of this signaling molecule, the FGF-2 gene was inactivated by homologous recombination in mouse embryonic stem cells. FGF-2-deficient mice are viable, but display cerebral cortex defects at birth. Bromodeoxyuridine pulse labeling of embryos showed that proliferation of neuronal progenitors is normal, whereas a fraction of them fail to colonize their target layers in the cerebral cortex. A corresponding reduction in parvalbumin-positive neurons is observed in adult cortical layers. Neuronal defects are not limited to the cerebral cortex, as ectopic parvalbumin-positive neurons are present in the hippocampal commissure and neuronal deficiencies are observed in the cervical spinal cord. Physiological studies showed that FGF-2-deficient adult mice are hypotensive. They respond normally to angiotensin II-induced hypertension, whereas neural regulation of blood pressure by the baroreceptor reflex is impaired. The present genetic study establishes that FGF-2 participates in controlling fates, migration and differentiation of neuronal cells, whereas it is not essential for their proliferation. The observed autonomic dysfunction in FGF-2-deficient adult mice uncovers more general roles in neural development and function.

Animals↗
PubMed1998

Renal haemodynamic responses to exogenous and endogenous adenosine in conscious dogs.

1. Adenosine has been suggested to be the mediator of a metabolic feedback mechanism which transfers acute changes in the tubular load into opposite changes in renal blood flow (RBF). The goal of the present experiments was to assess the importance of endogenously formed adenosine as a 'homeostatic metabolite' during short-term changes in metabolic demand. 2. In nine chronically instrumented conscious foxhounds, both the direct effects of adenosine injections (10, 30 and 100 nmol) into the renal artery and the temporal changes of RBF after short renal artery occlusions (15, 30 and 60 s duration), the most widely used experimental model to study the metabolic feedback mechanism in vivo, were studied. 3. Intrarenal bolus injections of adenosine (10, 30 and 100 nmol) induced dose-dependent decreases of RBF (RBF: -34 +/- 5, -59 +/- 4 and -74 +/- 4 %, respectively). This vasoconstrictor effect of adenosine was significantly larger (RBF: -51 +/- 4, -68 +/- 4 and -83 +/- 3 %, respectively) when the dogs received a low salt diet. 4. The post-occlusive responses were characterized by a transient hyperaemia with no detectable drop of RBF below the preocclusion level. The post-occlusive responses were affected neither by changes in local angiotensin II levels, nor by intrarenal infusions of hypertonic NaCl or blockade of A1 adenosine receptors. 5. When intrarenal adenosine levels were elevated by infusion of the adenosine uptake inhibitor dipyridamole, a transient, although weak, post-occlusive vasoconstriction was detected. 6. In summary, the present data demonstrate that adenosine acts as a potent renal vasoconstrictor in the conscious dog. The endogenous production of adenosine during short-lasting occlusions of the renal artery, however, appears to be too small to induce a post-occlusive vasoconstrictor response of RBF. These results suggest that a metabolic feedback with adenosine as 'homeostatic metabolite' is of minor importance in the short-term regulation of RBF in the conscious, unstressed animal.

Adenosine↗
PubMed1998

Autoregulation of renal blood flow in the conscious dog and the contribution of the tubuloglomerular feedback.

1. The aim of this study was to investigate the autoregulation of renal blood flow under physiological conditions, when challenged by the normal pressure fluctuations, and the contribution of the tubuloglomerular feedback (TGF). 2. The transfer function between 0.0018 and 0.5 Hz was calculated from the spontaneous fluctuations in renal arterial blood pressure (RABP) and renal blood flow (RBF) in conscious resting dogs. The response of RBF to stepwise artificially induced reductions in RABP was also studied (stepwise autoregulation). 3. Under control conditions (n = 12 dogs), the gain of the transfer function started to decrease, indicating improving autoregulation, below 0.06-0.15 Hz (t = 7-17 s). At 0.027 Hz a prominent peak of high gain was found. Below 0.01 Hz (t > 100 s), the gain reached a minimum (maximal autoregulation) of -6.3 +/- 0.6 dB. The stepwise autoregulation (n = 4) was much stronger (-19.5 dB). The time delay of the transfer function was remarkably constant from 0.03 to 0.08 Hz (high frequency (HF) range) at 1.7s and from 0.0034 to 0.01 Hz (low frequency) (LF) range) at 14.3 s, respectively. 4. Nifedipine, infused into the renal artery, abolished the stepwise autoregulation (-2.0 +/- 1.1 dB, n = 3). The gain of the transfer function (n = 4) remained high down to 0.0034 Hz; in the LF range it was higher than in the control (0.3 +/- 1.0 dB, P < 0.05). The time delay in the HF range was reduced to 0.5 s (P < 0.05). 5. After ganglionic blockade (n = 7) no major changes in the transfer function were observed. 6. Under furosemide (frusemide) (40 mg + 10 MG h-1 or 300 mg + 300 mg h-1 i.v..) the stepwise autoregulation was impaired to -7.8 +/- 0.3 or 6.7 +/- 1.9 dB, respectively (n = 4). In the transfer function (n = 7 or n = 4) the peak at 0.027 Hz was abolished. The delay in the LF range was reduced to -1.1 or -1.6 s, respectively. The transfer gain in the LF range (-5.5 +/- 1.2 or -3.8 +/- 0.8 dB, respectively) did not differ from the control but was smaller than that under nifedipine (P < 0.05). 7. It is concluded that the ample capacity for regulation of RBF is only partially employed under physiological conditions. The abolition by nifedipine and the negligible effect of ganglionic blockade show that above 0.0034 Hz it is almost exclusively due to autoregulation by the kidney itself. TGF contributes to the maximum autoregulatory capacity, but it is not required for the level of autoregulation expended under physiological conditions. Around 0.027 Hz, TGF even reduces the degree of autoregulation.

Animals↗
PubMed1998

Catheter-related infections in long-term catheterized dogs. Observations on pathogenesis, diagnostic methods, and antibiotic lock technique.

BACKGROUND: Intravascular catheters are associated with severe infections in patients, but only few reports on this problem in animal research exist. OBJECTIVE: We report on catheter-related bacterial colonization and its consequences in long-term catheterized animals. MATERIAL AND METHOD: Foxhounds were instrumented with intravascular catheters and flow probes to study the regulation of renal blood flow and pressures. RESULTS: After flushing the catheters, alterations in renal blood flow were observed and these could be related to bacterial colonization of intravascular catheters with Pseudomonas species. After attention had been focused on aseptic technique in all experimental phases and prophylactic antibiotic lock instituted, the occurrence of Pseudomonas bacteremia ceased, and the magnitude and incidence of catheter-related colonization and infection by Pseudomonas species dropped considerably. CONCLUSION: The catheter-related colonization that occurred spontaneously in these animals resembled findings in animal experiments in which catheter-related infections were deliberately induced as well as observations made with regard to catheter-related infections in patients. This report emphasizes the importance of asepsis when working with animals with long-term intravascular catheters. We suggest that monitoring for this complication, e.g., by means of catheter cultures at the time of removal, should routinely be part of protocols for animal experiments using long-term intravascular catheters.

Animals↗
PubMed1998

Cardiac remodelling in experimental renal failure--an immunohistochemical study.

BACKGROUND: In view of the high rate of cardiac death in renal failure, the factors involved in the genesis of structural changes in the heart are of obvious interest. The present study addresses the issue whether growth factors known to be involved in cardiac remodelling are abnormally expressed in rats with renal failure. METHODS: Sprague Dawley rats were subjected to binephrectomy (2 days) or subtotal nephrectomy (8 weeks). Controls were sham-operated rats and rats with Goldblatt hypertension. Cardiac expression of proliferating cellular nuclear antigen (PCNA), of growth factors and of their receptors (PDGF, TGF-beta, VEGF) was investigated immunohistochemically. In addition, cardiac PDGF-and TGF-beta mRNA were assessed using quantitative RT-PCR. RESULTS: Eight weeks after subtotal nephrectomy (SNX) significantly increased expression of PCNA and PDGF was found in the cardiac interstitium and of PCNA and VEGF in the walls of intramyocardial arteries. In addition, PCNA-positive cardiomyocytes were noted in SNX. Similar changes were not seen in the hearts of hypertensive controls, i.e. rats with renovascular hypertension, despite slightly higher blood pressure and more pronounced left ventricular hypertrophy (LVH). While significant changes of cardiac PDGF- and TGF-beta mRNA expression could not be documented in the whole-heart homogenates 8 weeks after subtotal nephrectomy, 2 days after bilateral nephrectomy PDGF mRNA was significantly increased and TGF-beta mRNA decreased. CONCLUSION: The observations demonstrate (i) specific activation of cardiac interstitial cells after SNX, (ii) activation of postmitotic cardiomyocytes, possibly predisposing to apoptosis, (iii) increased expression of PDGF in the cardiac interstitium and in the wall of intramyocardial arteries, (iv) increased expression of VEGF associated with hypertrophy of arterial smooth muscle cells. These results were not explained by elevated blood pressure or LVH, respectively.

Acute Kidney Injury↗
PubMed1998

Blood pressure variability and urine flow in the conscious dog.

Pressure-dependent urine production is considered to be a major factor in long-term blood pressure control. The phenomenon has been well characterized for fixed levels of renal perfusion pressure (RPP), but the influence of physiological fluctuations in RPP and spontaneous variations in renal blood flow (RBF) on short-term urine flow (UV) remain unclear. To clarify this issue, we studied the interdependence of RPP, RBF, and UV in 13 conscious foxhounds during a single-step pressure reduction, under normal conditions, and with induced pressure changes. Reducing RPP in a single step to approximately 80 mmHg revealed short response times of RBF (0.4 +/- 0.1 s, n = 7) as well as of UV (8.1 +/- 0.8 s, n = 7). Under control conditions, UV was coupled with spontaneous variations of RBF (r = 0.94, P < 0.001), in contrast to RPP, which showed no significant correlation with UV (r = 0.09, P = NS). To discern the pressure and blood flow dependency of UV at a reduced RPP, we induced 0.9-mHz blood pressure oscillations (80 +/- 10 mmHg), which phase shifted RPP and RBF. Conversely, under these conditions, UV was dependent on RPP (r = 0.95, P < 0.001). These results suggest that spontaneous fluctuations in RBF around a normal baseline level lead to concomitant changes in urine production, in contrast to physiological short-term oscillations in RPP, which are not correlated to changes in UV. However, during induced oscillations of perfusion pressure, the blood flow dependence was no longer observed and UV was entirely pressure dependent.

Animals↗
PubMed1997

Dissociation of left ventricular hypertrophy, beta-myosin heavy chain gene expression, and myosin isoform switch in rats after ascending aortic stenosis.

BACKGROUND: Reexpression of the fetal beta-myosin heavy chain (beta-MHC) gene was reported to be a marker for phenotypic reprogramming and cardiac hypertrophy in rats. Recent in vitro studies strongly suggested a role of angiotensin II for phenotypic reprogramming. In the present investigation, beta-MHC gene expression was studied in an experimental model of pressure-over-load hypertrophy that is not associated with a concurrent activation of the circulating renin-angiotensin system. METHODS AND RESULTS: Hypertrophy was induced in rats by ascending aortic banding (n = 40). After 7 days, myosin contained 31% (P < .05) of the beta-MHC isoform in banded but < 5% in sham-operated animals. However, no specific elevation of beta-MHC mRNA levels was found in banded animals. In contrast, hearts of rats with abdominal aortic banding displayed a marked increase in beta-MHC mRNA levels (3-fold to 5-fold, P < .05). Both the left ventricular weight and left ventricular peak systolic pressure were significantly elevated compared with sham-operated animals (abdominal aortic banding, +13% and 164 +/- 7 mm Hg; ascending aortic banding, +27% and 191 +/- 9 mm Hg). Plasma renin activity was elevated in rats with abdominal aortic banding (2.5-fold, P < .05) but not in rats with ascending aortic banding. CONCLUSIONS: The results of the present work do not support the concept that increased beta-MHC gene expression is a general "stable late marker" of myocardial hypertrophy in rats. Our results suggest that the stimulation of the renin-angiotensin system is crucial for the activation of the beta-MHC gene.

Analysis of Variance↗
PubMed1997

Baroreflex sensitivity and heart rate variability in conscious rats with myocardial infarction.

The baroreflex sensitivity (BRS) and the heart rate variability (HRV) were studied in conscious rats after myocardial infarction (MI; induced by coronary artery ligation) and after sham operation (SH). BRS was determined by linear regression of R-R interval vs. arterial pressure changes induced by nitroprusside or methoxamine (intravenous bolus). HRV was calculated from 3-min electrocardiogram recordings. Left ventricular end-diastolic pressure and plasma atrial natriuretic peptide were increased after MI; plasma norepinephrine and basal heart rate (HR) remained unchanged. At 3 and 28 days after MI, BRS was reduced as indicated by decreased reflex bradycardia (RB) (MI, 0.66 +/- 0.13 and 0.78 +/- 0.07 ms/mmHg; SH, 1.27 +/- 0.16 and 1.48 +/- 0.14 ms/mmHg, respectively; P < 0.05 MI vs. SH). At 56 days after MI, BRS was normalized. RB was unaffected by atropine 3 and 28 days after MI but reduced in all other groups. The increase of basal HR by atropine 3 and 28 days after MI was less than in all other groups. HRV (SD of mean N-N interval, coefficient of variance, low- and high-frequency power; studied at 28 and 56 days) was similar in all groups. It is concluded that BRS is transiently depressed in rats with left ventricular dysfunction after MI probably due to a reduced reflex vagal activity. Even though basal HR and HRV are unchanged after MI, a temporary attenuation of tonic vagal activity is unmasked after autonomic blockade.

Analysis of Variance↗
PubMed1997

Flow versus pressure in the control of renin release in conscious dogs.

In Goldblatt hypertension, renal artery stenosis reduces renal arterial pressure (RAP) and renal blood flow (RBF) and thereby increases plasma renin activity (PRA) levels. Although it is clear that reduction in RAP stimulates renin, the decrease in RBF may contribute to higher PRA as well. However, it has hitherto never been possible to dissociate a decrease in RBF from a concomitant decrease in RAP. To overcome this restriction, we used two protocols. 1) RAP was reduced in a single step to 70 +/- 0.2 mmHg (N = 8). RBF followed the sudden fall in RAP within 15 s but subsequently took on initial levels. In contrast, renal venous PRA increased from 0.95 +/- 0.22 to 5.6 +/- 1.4 ng angiotensin I.ml-1.h-1 (P < 0.05) and remained at higher values even after RBF had regained control conditions. 2) Resonance between RAP and RBF was induced by superimposing slow sinusoidal RAP waves with a period length of 450 s (N = 9), leading to a phase shift of roughly 180 degrees (time delay, 241 +/- 12 s), i.e., RBF was maximal at minimal RAP. Under these conditions, renin release was only dependent on decrements in RAP (delay of only 27 +/- 8 s). In conclusion, RBF played no major role in renin release.

Animals↗
PubMed1996

Blood-pressure variability is buffered by nitric oxide.

The baroreflex constitutes the only hitherto known buffer of rapid blood pressure oscillations. In order to investigate the influence of nitric oxide (NO) and the sinoaortic and cardiopulmonary baroreflex pathways on the dynamic properties of blood pressure control, we determined the power spectra of 24-h blood pressure time series of conscious dogs. This was done in the intact state (n = 6), during blockade of NO synthesis via the false substrate NG-nitro-L-arginine ((L-NNA), 16.5 +/- 2 mg/kg body weight i.v., n = 5) and in animals devoid of baroreceptor reflexes (n = 5). After L-NNA, blood pressure (BP) increased by roughly 20 mmHg to 137 +/- 6 mmHg (P < 0.01), heart rate decreased from 97 +/- 6 to 68 +/- 3 beats/min (P < 0.01). The power of blood pressure variations within the frequency range 0.1-0.5 Hz was tripled by L-NNA (P < 0.05). By comparison total sinoaortic and cardiopulmonary denervation increased power of slower oscillations ( < 0.1 Hz) by a factor of 4.7 (P < 0.05). Thus, NO and the baroreceptor reflex both play an important role as physiological blood pressure buffers, NO for rapid (0.1-0.5 Hz) and the baroreflex for slower fluctuations ( < 0.1 Hz).

Animals↗
PubMed1995

Subunit-specific inhibition of inward-rectifier K+ channels by quinidine.

Distinct inward-rectifier K+ channel subunits were expressed in Xenopus oocytes and tested for their sensitivity to the channel blocker quinidine. The 'strong' inward-rectifier K+ channel IRK1 was inhibited by quinidine with an EC50 of 0.7 mM, while the 'weak' rectifier channel ROMK1 was only moderately inhibited. ROMK1(N171D)-IRK1C-term chimeric channels, which carry both sites for strong rectification of IRK1 channels (the negatively charged D171 in the second transmembrane domain and the IRK1-C-terminus including E224), displayed strong rectification like IRK1, but showed weak sensitivity to quinidine-like ROMK1, suggesting independence of quinidine binding and rectification mechanisms. Moreover, BIR10 and BIR11, two strong rectifier subunits originally cloned from rat brain, exerted subunit-specific sensitivity to quinidine, being much higher for BIR11. Quinidine blockade of IRK1 was not voltage-dependent, but strongly dependent on the pH in the superfusate. These results strongly suggest a subunit-specific interaction of inward-rectifier K+ channels with neutral quinidine within membrane lipid bilayers.

Animals↗
PubMed1995

On the origin of low-frequency blood pressure variability in the conscious dog.

1. Baroreceptor denervation increases blood pressure variability below 0.1 Hz. This study was undertaken to determine to what extent these fluctuations originate from the central nervous system or from cardiovascular sources. 2. Blood pressure was recorded at a rate of 10 Hz for approximately 3.5 h in conscious, resting dogs. Power density spectra were calculated from all 2(17) points of each recording session and integrated between 0.0002 and 0.1 Hz. 3. Blockade of the afferent limb of the baroreceptor reflex by surgical denervation of sinoaortic and cardiopulmonary afferents (Den; n = 6) significantly increased integrated power more than sixfold compared with a control group (n = 11). 4. Impairment of the efferent limb in non-deafferented dogs by either alpha 1-adrenergic blockade with prazosin (Praz; n = 7) or ganglionic blockade with hexamethonium (Hex; n = 6) failed to raise variability. 5. Both prazosin (n = 6) and hexamethonium (n = 3) reduced the increased variability in denervated dogs. 6. In non-deafferented dogs receiving hexamethonium, elevation of mean blood pressure to the hypertensive level of the Den group, by a continuous infusion of noradrenaline (n = 4), did not change the variability. 7. It is concluded that in the absence of changes in posture, most of the increased blood pressure variability after baroreceptor denervation is derived from the central nervous system. 8. Direct comparison of power spectra of the Den (total variability) and Hex groups (variability derived from the cardiovascular system only) suggests that the central nervous system is also the prevalent source of low-frequency blood pressure variability in intact animals.

Animals↗
PubMed1995

Modulation of erythropoietin formation by changes in blood volume in conscious dogs.

1. A possible influence of the filling of the circulatory system on the plasma concentration of erythropoietin, which is the major regulator of erythrocyte formation, was investigated in conscious dogs. 2. Over an experimental period of 5 h, the animals were subjected to either haemorrhage (hypovolaemia), blood volume expansion (hypervolaemia), or exchange transfusion of blood with dextran (isovolaemic anaemia). 3. A reduction of blood volume by 20% induced by haemorrhage increased plasma erythropoietin levels approximately 1.5-fold in the absence of significant changes in haematocrit. 4. An expansion of blood volume by 12% induced by an intravenous infusion of dextran did not change plasma erythropoietin levels, although the haematocrit decreased by 0.04. 5. A reduction of the haematocrit by 0.12 in the absence of changes in blood volume induced by an isovolaemic exchange transfusion (dextran vs. blood) increased plasma erythropoietin levels approximately 3-fold. 6. Total renal oxygen supply did not change in any of the three experimental protocols. 7. These data indicate that in dogs the erythropoietin production rate is modulated by changes in blood volume, and suggest a possible role of erythropoietin in the regulation of blood volume.

Anemia↗