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.

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.

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.

Abstract 064: 20-HETE Contributes to Vasoconstriction of Renal Microvessels and Sodium Retention in Cyp4a14-/- Mice, a Model of 20-HETE Dependent Hypertension

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Ankit Gilani ◽  
Varunkumar Pandey ◽  
Joseph Zullo ◽  
Priyanka Mishra ◽  
John R Falck ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Isotonic Saline ◽  
Urinary Sodium Excretion ◽  
Water Soluble ◽  
Arachidonic Acid Metabolite ◽  
Male Mice ◽  
Kidney Weight ◽  
Doppler Flowmetry ◽  
In The Wild

20-HETE (20-Hydroxyeicosatetraenoic acid), is a cytochrome P450 (CYP) 4A-derived arachidonic acid metabolite. 20-HETE has been linked to both pro-hypertensive (via increased vasoconstriction, vascular remodeling and vascular injury of renal microvessels) and anti-hypertensive (inhibiting ion transport in the distal nephron) functions. In this study we examined the effect of 20-SOLA (2,5,8,11,14,17-hexaoxanonadecan-19-yl-20-hydroxyeicosa-6(Z),15(Z)-dienoate), a water soluble antagonist of the actions of 20-HETE on renal hemodynamics and sodium (Na) excretion in Cyp4a14 knockout (CYP4a14-/-) male mice. The CYP4a14-/- male mice display hypertension accompanied by increased vascular 20-HETE levels. Administration of 20-SOLA (10mg/kg/day in drinking water) normalized blood pressure (BP) in male Cyp4a14-/- mice at day 10 of treatment (124±1 vs. 153±2 mmHg in untreated male Cyp4a14-/- mice; p<0.05). The normalization of blood pressure was accompanied by transient increase in the urinary sodium excretion in the Cyp4a14-/- male mice (8.3±0.7 vs. 5.8±0.5 μmol/g body weight/day; p<0.05). Importantly, 20-SOLA increased glomerular filtration rate (GFR) of Cyp4a14-/- mice (2.38±0.05 vs. 1.88±0.18 μL/min/mg kidney weight, p<0.05) as opposed to no changes observed in the wild type (WT: (2.26±0.18 vs. 2.33±0.20μL/min/mg kidney weight). Evaluation of the renal blood flow (RBF) by laser Doppler flowmetry showed that treatment with 20-SOLA increased the RBF in Cyp4a14-/- mice by 12.3±4%, which remained unaltered in the WT. Additionally, the pressure-induced myogenic tone of isolated preglomerular microvessels was significantly elevated in Cyp4a14-/- mice; 20-SOLA treatment prevented the increase in myogenic responses. The natriuretic response to an isotonic saline loading challenge (10% of body weight, IP) was significantly attenuated in the Cyp4a14-/- mice as compared to the WT (35.5±2.8 vs. 57.4±8.3 percentage of Na load, p<0.05); this was corrected by 20-SOLA (61.7±5.7 percentage of Na load, p<0.05). These results confirm that 20-SOLA normalizes blood pressure of Cyp4a14-/- male mice and demonstrates that this is associated with increases in GFR, RBF and natriuresis.

Abstract P276: A High Sodium Diet Reduces Cutaneous Microvascular Function In Normotensive Individuals With Salt Sensitive Blood Pressure

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Jordan C Patik ◽  
Joseph M Stock ◽  
Nathan T Romberger ◽  
Shannon L Lennon ◽  
William B Farquhar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Sodium Intake ◽  
Local Heating ◽  
Urinary Sodium Excretion ◽  
Microvascular Function ◽  
Dietary Sodium ◽  
Heating Unit ◽  
Doppler Flowmetry ◽  
High Sodium

Impaired vascular function likely contributes to the association between dietary sodium intake and the development of cardiovascular disease. Using the cutaneous microvasculature as a model, we have previously shown that a high sodium (HS) diet blunts local heating-induced vasodilation in normotensive individuals with salt resistant (SR) blood pressure (BP). However, the effect of a HS diet on the cutaneous microvasculature in normotensive salt sensitive (SS) individuals remains unclear. Therefore, we tested the hypothesis that cutaneous microvascular function is reduced by a HS diet to a greater degree in SS compared to SR individuals. After each 7-day controlled feeding diet (low sodium (LS) = 20 mmol/day; HS = 300 mmol/day), an intradermal microdialysis fiber was inserted in the ventral forearm and perfused with Ringer’s solution. Skin blood flow (SkBF) was continuously monitored via laser Doppler flowmetry and a local heating unit was placed over the fiber and heated to 42°C until SkBF reached a stable plateau. Site-specific maximal SkBF was determined by perfusing 28mM sodium nitroprusside and heating to 43°C. Mean arterial pressure (MAP) was assessed at regular intervals on the contralateral arm and was used to calculate cutaneous vascular conductance (CVC = SkBF / MAP). Subjects wore a 24-hr ambulatory BP monitor and collected their urine on the final day of each diet. Fourteen subjects (9W / 5M, 42 ± 14 yr) whose MAP increased >5 mmHg (Δ8 ± 1 mmHg) on the HS diet were defined as SS and were compared to 14 age- (43± 14 yr) and sex-matched SR subjects (Δ1 ± 3 mmHg). SS and SR had similar MAP at baseline (88 ± 9 vs. 90 ± 8 mmHg, P = 0.88) and urinary sodium excretion was increased similarly across groups by the HS diet (Δ239 ± 104 vs. Δ220 ± 66 mmol / 24 hr, P = 0.20). Cutaneous vasodilation in response to local heating was decreased on the HS diet relative to the LS diet in both SS (Δ-9 ± 9 %CVCmax, P = 0.005) and SR (Δ-9 ± 9 %CVCmax, P=0.005); however, there was not a group x diet interaction (P = 0.99). In contrast to our hypothesis, these results suggest that the deleterious effects of high sodium diets on cutaneous microvascular function are similar in normotensive salt sensitive and salt resistant individuals.

Effects of l-arginine on systemic and renal haemodynamics in conscious dogs

1991 ◽  
Vol 81 (6) ◽  
pp. 727-732 ◽  
Author(s):  
Marohito Murakami ◽  
Hiromichi Suzuki ◽  
Atsuhiro Ichihara ◽  
Mareo Naitoh ◽  
Hidetomo Nakamoto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Renal Haemodynamics ◽  
Conscious Dogs ◽  
Arginine Infusion ◽  
Arterial Blood

1. The effects of l-arginine on systemic and renal haemodynamics were investigated in conscious dogs. l-Arginine was administered intravenously at doses of 15 and 75 μmol min−1 kg−1 for 20 min. 2. Mean arterial blood pressure, heart rate and cardiac output were not changed significantly by l-arginine infusion. However, l-arginine infusion induced a significant elevation of renal blood flow from 50 ± 3 to 94 ± 12 ml/min (means ± sem, P < 0.01). 3. Simultaneous infusion of NG-monomethyl-l-arginine (0.5 μmol min−1 kg−1) significantly inhibited the increase in renal blood flow produced by l-arginine (15 μmol min−1 kg−1) without significant changes in mean arterial blood pressure or heart rate. 4. Pretreatment with atropine completely inhibited the l-arginine-induced increase in renal blood flow, whereas pretreatment with indomethacin attenuated it (63 ± 4 versus 82 ± 10 ml/min, P < 0.05). 5. A continuous infusion of l-arginine increased renal blood flow in the intact kidney (55 ± 3 versus 85 ± 9 ml/min, P < 0.05), but not in the contralateral denervated kidney (58 ± 3 versus 56 ± 4 ml/min, P > 0.05). 6. These results suggest that intravenously administered l-arginine produces an elevation of renal blood flow, which may be mediated by facilitation of endogenous acetylcholine-induced release of endothelium-derived relaxing factor and vasodilatory prostaglandins.

Vasoactive intestinal polypeptide reduces hydrochloric acid-induced duodenal mucosal permeability

1993 ◽  
Vol 264 (2) ◽  
pp. G272-G279 ◽  
Author(s):  
O. Nylander ◽  
E. Wilander ◽  
G. M. Larson ◽  
L. Holm
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Vasoactive Intestinal Polypeptide ◽  
Lesion Score ◽  
Morphological Examination ◽  
Mucosal Permeability ◽  
Doppler Flowmetry ◽  
Arterial Blood ◽  
51Cr Edta ◽  
Intestinal Polypeptide

The duodenum in anesthetized rats was perfused with HCl, and mucosal integrity was assessed by measuring the clearance of 51Cr-labeled EDTA from blood to lumen and/or by morphological examination (lesion score). Duodenal blood flow was determined by laser Doppler flowmetry and luminal alkalinization as well as H+ disappearance by backtitration. Intravenous infusion of vasoactive intestinal polypeptide (VIP; 13.5 micrograms.kg-1.h-1) increased luminal alkalinization threefold and decreased clearance of 51Cr-EDTA by 50%. VIP also decreased arterial blood pressure and induced a small and irregular decrease in duodenal blood flow. Perfusion with 10 mM HCl increased clearance of 51Cr-EDTA 2.1-fold, but the lesion score was not different from that in saline-perfused animals. Perfusion with 20 mM HCl increased clearance of 51Cr-EDTA four-fold and induced a greater lesion score than did 10 mM. Perfusion with either 10 or 20 mM HCl did not affect the duodenal blood flow. VIP reduced the rise in clearance of 51Cr-EDTA in response to 10 mM but not that to 20 mM HCl. Intravenous injection of prazosin (50 micrograms/kg) decreased luminal alkalinization, clearance of 51Cr-EDTA, blood pressure, and duodenal blood flow. In prazosin-pretreated rats, perfusion with 10 mM HCl increased clearance of 51Cr-EDTA 2.6-fold, and the lesion score was greater in this group than in animals infused with VIP. A positive linear correlation was obtained between HCO3- secretion and the mean rate of H+ disappearance.(ABSTRACT TRUNCATED AT 250 WORDS)

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