Role of Haematocrit in Mediating the Actions of Chronic Erythropoietin Treatment on Blood Pressure and Renal Haemodynamics in the Rat

1993 ◽  
Vol 85 (6) ◽  
pp. 717-724 ◽  
Author(s):  
Chunlong Huang ◽  
Gerard Davis ◽  
Edward J. Johns
Keyword(s):  
Blood Pressure ◽  
Direct Action ◽  
Chronic Administration ◽  
Treated Group ◽  
Recombinant Erythropoietin ◽  
Doppler Flowmetry ◽  
Human Recombinant Erythropoietin ◽  
Vascular Responsiveness ◽  
Erythropoietin Treatment ◽  
Renal Vascular

1. This investigation aimed to study the effect of chronic administration of human recombinant erythropoietin on haematocrit, blood pressure, renal cortical and papillary resistances and vascular responsiveness to vasoconstrictor agents. 2. Rats were treated with placebo or 25, 50 or 100 units/kg erythropoietin subcutaneously, every other day for 3 weeks. Animals were then anaesthetized with sodium pentobarbitone and were prepared for laser-Doppler flowmetry measurement in the renal cortex and papilla. 3. Haematocrit in the placebo-treated group was 48.0 + 0.5% and was raised to 52.5 + 0.7, 55.9 + 0.8 and 62.4 + 1.1% (all P <0.05) by the chronic administration of 25, 50 and 100 units/kg doses of the hormone, respectively. Blood pressure was 107 + 1 mmHg in the placebo-treated group and was elevated to 116 + 2 and 130 + 1 mmHg (both P <0.05), respectively, by the two highest doses of erythropoietin. Cortical and papillary perfusions were reduced at the highest dose of erythropoietin, but calculated resistances were increased by 15 and 40% (P <0.05) at 50 and 100 units/kg doses of the hormone, respectively. 4. Infusion of the vasopressor hormones vasopressin and phenylephrine caused increases in blood pressure and decreases in renal cortical and papillary perfusion, the magnitudes of which were only marginally changed by the highest dose of the erythropoietin. Angiotensin II increased blood pressure and decreased cortical perfusion, and the magnitudes of these responses were unchanged by the chronic treatment with erythropoietin. 5. Acute graded increases in haematocrit resulted in significantly (P <0.05) raised blood pressure above a value of 58%. However, renal cortical and papillary perfusions decreased and resistances were increased significantly (P <0.05) when the haematocrit was raised above 56%. 6. The acute transfusion study demonstrated that elevations in blood pressure and renal vascular resistances occurred at haematocrit values somewhat higher than when it was raised by chronic erythropoietin treatment. Thus this would be consistent with the suggestion that erythropoietin has some direct action on the vasculature beyond that resulting from the raised haematocrit. These data show that a low dose regimen of erythropoietin can modestly increase haematocrit without other cardiovascular changes becoming apparent. The findings add weight to the recent clinical practice of using very low doses of the hormone in the treatment of chronic renal failure.

Study of the actions of human recombinant erythropoietin on rat renal haemodynamics

1992 ◽  
Vol 83 (4) ◽  
pp. 453-459 ◽  
Author(s):  
Chunlong Huang ◽  
Gerard Davis ◽  
Edward J. Johns
Keyword(s):  
Blood Pressure ◽  
Chronic Administration ◽  
Renal Haemodynamics ◽  
Marginal Effect ◽  
Recombinant Erythropoietin ◽  
Doppler Flowmetry ◽  
Human Recombinant Erythropoietin ◽  
Sustained Reduction ◽  
Anaesthetized Rat ◽  
Cortical Perfusion

1. Studies were undertaken to examine the effect of acute and chronic administration of human recombinant erythropoietin on kidney cortical and papillary perfusion in the anaesthetized rat using laser-Doppler flowmetry. 2. Thirty minutes after erythropoietin (50 and 150 units/kg intravenously), blood pressure, cortical perfusion and papillary perfusion were unchanged. 3. In animals treated chronically with erythropoietin over 7 days (three doses of 150 units/kg subcutaneously) blood pressure was similar to that of vehicle-treated animals, whereas cortical perfusion and papillary perfusion were reduced by 23% and 20%, respectively (both P<0.05), and the packed cell volume (51.1 ± 0.7%) was significantly (P<0.01) greater than in vehicle-treated animals (46.2 ± 0.6%). 4. Bolus doses of vasopressin and phenylephrine increased blood pressure (by between 10% and 40%) and decreased cortical and papillary perfusion (by between 10% and 20%), while angiotensin II caused similar increases in blood pressure and decreases in cortical perfusion but not papillary perfusion. The magnitude and pattern of these responses were comparable after both acute and chronic administration of erythropoietin. 5. Erythropoietin given acutely at therapeutic levels has a marginal effect on cortical and papillary perfusion. However, the chronic treatment indicated that there was a sustained reduction in both cortical and papillary perfusion, reflecting a vasoconstriction. This reduction in renal haemodynamics could contribute to the increase in blood pressure observed when this hormone is administered in man.

Thyroidal vascular responsiveness to parasympathetic stimulation is increased in hyperthyroidism

1993 ◽  
Vol 264 (3) ◽  
pp. E398-E402 ◽  
Author(s):  
M. Dey ◽  
M. Michalkiewicz ◽  
L. J. Huffman ◽  
G. A. Hedge
Keyword(s):  
Blood Flow ◽  
Sympathetic Nerves ◽  
Treated Group ◽  
Receptor Activation ◽  
Vascular Conductance ◽  
Doppler Flowmetry ◽  
Pretreated Group ◽  
Vascular Responsiveness ◽  
Stimulation Of

It has been suggested that thyroid blood flow (TBF) is regulated by both parasympathetic and sympathetic nerves. Because thyroxine (T4) pretreatment increases the sensitivity of the thyroid to the effects of thyrotropin, the present study was conducted to determine whether T4 pretreatment can also sensitize the thyroid to the effect of parasympathetic stimulation on TBF. Untreated or T4-pretreated rats were anesthetized, and both superior laryngeal nerves (SLN) were transected. TBF was continuously monitored by laser Doppler flowmetry (LDF), and thyroid vascular conductance (TVC) was also determined by the microsphere technique. Stimulation of the SLN had no effect on TBF or TVC in untreated rats when measured by LDF or microspheres. In contrast, stimulation of the SLN after T4 pretreatment increased TBF by 65 +/- 21% over prestimulus levels as measured by LDF. TVC was also increased significantly (P < 0.05) in these rats compared with TVC in a nonstimulated T4-pretreated group. To examine the role of muscarinic receptor activation in the mediation of these increases in TVC, T4 pretreated rats were given saline or atropine prior to SLN transection. Stimulation of the SLN in T4-pretreated rats given saline increased TVC significantly (P < 0.05) compared with TVC in the nonstimulated saline-treated or atropine-treated group. In contrast, TVC in the stimulated group given saline was not significantly different from the group that was stimulated after atropine injection. Our results suggest that the thyroidal vascular responsiveness to parasympathetic stimulation is increased in the hyperthyroid condition.

Absence of Adrenergic Mediation of Agonist Response to [Sar1,Ala8]Angiotensin II in Conscious Normotensive and Hypertensive Dogs

1979 ◽  
Vol 57 (1) ◽  
pp. 71-81 ◽  
Author(s):  
B. G. Zimmerman
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Intravenous Infusion ◽  
Direct Action ◽  
Renal Vascular Resistance ◽  
Angiotensin Receptors ◽  
Conscious Dog ◽  
Renal Vascular

1. In the conscious normotensive and two-kidney Goldblatt hypertensive dog a transient agonist response to the intravenous infusion of saralasin (1 μg min−1 kg−1) was manifested by a small increase in blood pressure (6–12 mmHg) and 28–30% increase in renal vascular resistance. 2. These increases in blood pressure and renal vascular resistance were unaffected by administration of either phentolamine or guanethidine. 3. The agonist response in the conscious dog is most likely accounted for by a direct action of saralasin on vascular angiotensin receptors.

Abstract 266: Renovascular Remodeling in Hypertensive Dahl-SS Rats: Role of MMP Inhibitor as a Hypertension Ameliorating Agent

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sourav Kundu ◽  
Sathnur Pushpakumar ◽  
Naira Metriveli ◽  
Suresh C Tyagi ◽  
Utpal Sen
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Vascular Density ◽  
High Salt Diet ◽  
Doppler Flowmetry ◽  
Cortical Blood Flow ◽  
Mmp Inhibitor ◽  
Arterial Blood ◽  
Renal Cortical Blood Flow ◽  
Renal Vascular

High salt diet has long been associated with chronic hypertension. The development of renal injury in Dahl salt-sensitive (SS) hypertensive rats is characterized by structural and functional changes involving vascular remodeling. Increased activity of matrix metalloproteinases (MMPs) leading to alteration in the extracellular matrix (ECM) is the main mechanism contributing to increased peripheral vascular resistance. In this study, we hypothesized that inhibition of MMPs will modulate ECM remodeling by decreasing MMP activity and thus reduce mean arterial blood pressure. METHODS: We used Dahl-salt sensitive (Dahl-SS) and Lewis rats fed on high salt diet. The groups were 1) Dahl-SS, 2) Dahl-SS+GM6001 (non-specific MMP inhibitor), 3) Lewis, and 4) Lewis+GM6001. GM6001 was given at 0.5mg/mL by intra-peritoneal injection on alternate days for 3 weeks. Blood pressure, laser doppler flowmetry for renal cortical blood flow and barium angiography for renal vascular density were measured. Results: Mean arterial blood pressure was 172.10 ± 0.57 mm Hg in hypertensive Dahl-SS rats compared to 136.12 ± 1.22 mm Hg in Dahl-SS+GM6001 rats. The mean arterial pressures in lewis and lewis+GM6001 groups were 97.08 ± 0.56 and 87.63 ± 2.93 mm Hg respectively. Laser doppler flowmetry showed reduced renal cortical blood flow (1333.33 flux units) in Dahl-SS rats compared to Dahl-SS rats treated with GM6001 (1605 flux units). Lewis rats showed similar renal cortical flow with (1488.33 flux units) or without GM6001 (1425 flux units). Barium angiography demonstrated increased renal vascular density with patent branches in the renal cortex of animals treated with MMP inhibitor, GM6001. Conclusion: Our results suggest that in hypertensive Dahl-SS rats, inhibition of MMP attenuates high blood pressure, maintains patency of renal cortical vessels thus improving cortical blood flow.

scholarly journals Recombinant erythropoietin treatment does not alter the blood pressure despite elevated haematological parameters in normotensive Wistar rats

2020 ◽  
Vol 71 (2) ◽  
pp. 2157
Author(s):  
F. SULTAN ◽  
B.A. GANAIE ◽  
D.M. MIR ◽  
J.A. DAR
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Wistar Rats ◽  
Behavioural Change ◽  
Systemic Blood Pressure ◽  
Haematological Parameters ◽  
Recombinant Erythropoietin ◽  
Short Term ◽  
Systemic Blood ◽  
Erythropoietin Treatment

Use of erythropoietin (EPO) is believed to be associated with adverse cardiovascular events, especially high blood pressure. Also, its illegal use in blood doping is thought to result in detrimental events both in humans and equines. To test this hypothesis, normal Wistar rats were treated with recombinant erythropoietin (rEPO @ 400 i.u/kg s.c) or normal saline one day apart for one week. Heart rate, systolic, diastolic, mean arterial pressure and blood count were determined. Rats were also observed for their behaviour during the study period. rEPO significantly (P<0.001) increased the erythrocyte count (RBC), haemoglobin (Hb), hematocrit (HCT) and platelet count (PLT) in comparison to control animals. Despite such an increase in hematocrit which in turn increases blood viscosity, the systemic blood pressure and heart rate did not differ between the groups. rEPO treatment did not cause any untoward behavioural change in animals. In conclusion, despite the profound effect on haematological parameters (especially hematocrit), rEPO was without any effect on blood pressure and heart rate and the hypothesis of short-term erythropoietin-induced alterations in cardiac parameters was not verified.

Chronic Administration of Octreotide Increases Vascular Responsiveness in Rats with Portal Hypertension

1996 ◽  
Vol 91 (5) ◽  
pp. 601-606 ◽  
Author(s):  
Yi-Tsau Huang ◽  
Ju-Fen Tsai ◽  
Tsun-Bin Liu ◽  
Chuang-Ye Hong ◽  
May C.-M. Yang ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Mesenteric Artery ◽  
Portal Pressure ◽  
Chronic Administration ◽  
Treated Group ◽  
Contractile Responses ◽  
Vascular Responsiveness ◽  
Octreotide Treatment ◽  
Vehicle Treated Group

1. It has been reported that octreotide partially corrects the hyperdynamic state in patients and animals with portal hypertension. The aim of the present study was to investigate whether chronic administration of octreotide can increase vascular responsiveness in rats with portal hypertension. 2. Portal hypertension was induced by partial portal vein ligation. Octreotide was given for 9 days subcutaneously (100 μg/kg every 12 h) starting 1 day before ligation. The aorta and mesenteric artery were then removed to study contraction after pressure recording. 3. Octreotide treatment significantly reduced portal pressure and plasma glucagon concentrations compared with the vehicle-treated group. Both phenylephrine and vasopressin induced concentration-dependent contractile responses in the aorta and mesenteric artery from both groups. The maximum contractile responses to phenylephrine and vasopressin in aorta and mesenteric artery were significantly greater in the octreotide-treated group than in the vehicle-treated group. The EC50 values for phenylephrine and vasopressin were significantly different in the aorta, but not in the mesenteric artery, between the two groups. In contrast, octreotide treatment did not alter the contractile responsiveness of arteries from sham-operated rats. 4. These results show that, in rats with portal vein stenosis, octreotide increases arterial contractile responsiveness and reduces portal pressure.

Nitric oxide-dependent pulmonary vasodilation in polycythemic rats

2000 ◽  
Vol 279 (5) ◽  
pp. H2382-H2389 ◽  
Author(s):  
Benjimen R. Walker ◽  
Thomas C. Resta ◽  
Leif D. Nelin
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Treated Group ◽  
Vehicle Group ◽  
Recombinant Erythropoietin ◽  
Enos Expression ◽  
Human Recombinant Erythropoietin ◽  
Pulmonary Vasodilation ◽  
Isolated Lungs ◽  
Nitrite Nitrate

Polycythemia causes increased vascular production of nitric oxide (NO), most likely secondary to an effect of elevated vascular shear stress to enhance expression of endothelial nitric oxide synthase (eNOS). Because both polycythemia and increased eNOS expression are associated with chronic hypoxia-induced pulmonary hypertension, experiments were performed to test the hypothesis that increased hematocrit leads to upregulation of pulmonary eNOS and enhanced vascular production of NO independent of hypoxia. Rats were administered human recombinant erythropoietin (rEpo; 48 U/day) or vehicle for 2 wk. At the time of study, hematocrit was significantly greater in the rEpo-treated group than in the vehicle group (65.8 ± 0.7% vs. 45.1 ± 0.5%), although mean pulmonary artery pressure did not differ between treatments. Experiments on isolated, saline-perfused lungs demonstrated similar vasodilatory responses to the endothelium-derived NO-dependent agonist ionomycin in each group. Additional experiments showed that the vasoconstrictor response to the thromboxane mimetic U-46619 was diminished at lower doses in lungs from the rEpo group compared with the vehicle group. However, perfusate nitrite/nitrate concentration after 90 min of perfusion in isolated lungs was not different between groups. Additionally, no difference was detected between groups in lung eNOS levels by Western blot. We conclude that the predicted increase in shear stress associated with polycythemia does not result in altered pulmonary eNOS expression.

scholarly journals Resveratrol Protects Cardiac Tissue in Experimental Malignant Hypertension Due to Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Properties

2021 ◽  
Vol 22 (9) ◽  
pp. 5006
Author(s):  
Jelica Grujić-Milanović ◽  
Vesna Jaćević ◽  
Zoran Miloradović ◽  
Djurdjica Jovović ◽  
Ivica Milosavljević ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Diseases ◽  
Cardiac Tissue ◽  
Morphological Changes ◽  
Chronic Administration ◽  
Heart Tissue ◽  
Severe Form ◽  
Malignant Hypertension ◽  
Experimental Hypertension ◽  
Resveratrol Treatment

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.

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