Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

Renal parathyroid hormone (PTH) action is often studied at high doses (100 μg PTH/kg) that lower mean arterial pressure significantly, albeit transiently, complicating interpretation of studies. Little is known about the effect of acute hypotension on proximal tubule Na+ transporters. This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 μg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-Pi cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 ± 3 to 78 ± 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (<2 min) decreased arterial blood pressure to 51 ± 3 mmHg, decreased urine output, and shifted NHE3 and NaPi2 out of the low-density membranes enriched in apical markers. PTH at much lower doses (<1.4 μg·kg−1·h−1) did not change blood pressure and was diuretic. In conclusion, acute hypotension per se increases proximal tubule Na+ reabsorption without changing NHE3 or NaPi2 subcellular distribution, indicating that trafficking of transporters to the surface is not the likely mechanism; in comparison, hypotension secondary to high-dose PTH blocks the primary diuretic effect of PTH but does not inhibit the PTH-stimulated redistribution of NHE3 and NaPi2 to the base of the microvilli.

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The potential role of myosin motor proteins in mediating the subcellular distribution of NHE3 in the renal proximal tubule

AJP Renal Physiology ◽

10.1152/ajprenal.00577.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. F986-F992

Author(s):

Renato O. Crajoinas ◽

Juliano Z. Polidoro ◽

Adriana C. C. Girardi

Keyword(s):

Blood Pressure ◽

Proximal Tubule ◽

Subcellular Distribution ◽

Potential Role ◽

Renal Proximal Tubule ◽

Current Evidence ◽

Myosin Vi ◽

Arterial Blood ◽

Myosin Iia

Isoform 3 of the Na+/H+ exchanger (NHE3) is responsible for the majority of the reabsorption of NaCl, NaHCO3, and, consequently, water in the renal proximal tubule. As such, this transporter plays an essential role in acid-base balance and extracellular fluid volume homeostasis and determining systemic arterial blood pressure levels. NHE3 activity is modulated by a number of mechanisms, including the redistribution of the transporter between the body of the microvilli (where NHE3 is active) and the base of the microvilli (where NHE3 is less active). Although the physiological, pathophysiological, and pharmacological importance of the subcellular distribution of NHE3 has been well established, the exact mechanism whereby NHE3 is translocated along microvilli microdomains of the proximal tubule apical membrane is unknown. Nonmuscle myosin IIA and unconventional myosin VI move cargoes in anterograde and retrograde directions, respectively, and are known to redistribute along with NHE3 in the proximal tubule in response to a variety of natriuretic and antinatriuretic stimuli, including stimulation or inhibition of the renin-angiotensin system, high dietary Na+ intake, and high blood pressure. Therefore, this review aims to discuss the current evidence that suggests a potential role of myosin IIA and myosin VI in mediating the subcellular distribution of NHE3 along the kidney proximal tubule microvilli and their possible contribution in modifying NHE3-mediated Na+ reabsorption under both physiological and pathophysiological conditions.

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Epidural Clonidine or Bupivacaine as the Sole Analgesic Agent during and after Abdominal Surgery

Anesthesiology ◽

10.1097/00000542-199905000-00020 ◽

1999 ◽

Vol 90 (5) ◽

pp. 1354-1362 ◽

Cited By ~ 35

Author(s):

Marc De Kock ◽

Philippe Gautier ◽

Athanassia Pavlopoulou ◽

Marc Jonniaux ◽

Patricia Lavand'homme

Keyword(s):

High Dose ◽

General Anesthetics ◽

Visual Analogue Pain ◽

Pain Scores ◽

Arterial Blood ◽

Sedation Scores ◽

Group 3 ◽

Group 2 ◽

High Doses ◽

Group 1

Background The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine. Methods Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device. Results During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P < 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P < 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P < 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively. Conclusion Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.

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Abstract 507: Dual AT1 Receptor/Neprilysin (NEP) Inhibition (ARNI) vs. AT1 Receptor Blockade in TGR(mRen2)27 Rats: The More NEP Inhibition The Better?

Hypertension ◽

10.1161/hyp.64.suppl_1.507 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Lodi C Roksnoer ◽

Joep H van Esch ◽

Richard van Veghel ◽

Ingrid M Garrelds ◽

Usha M Bhaggoe ◽

...

Keyword(s):

Blood Pressure ◽

Vascular Reactivity ◽

Weight Ratio ◽

At1 Receptor ◽

Mesenteric Arteries ◽

Heart Weight ◽

Sodium Reabsorption ◽

High Dose ◽

Arterial Blood ◽

Nep Inhibition

Objective: Neprilysin inhibitors (NEPi) prevent the breakdown of natriuretic peptides, promoting vasodilation and natriuresis. However, they also increase angiotensin and endothelin-1 (ET1). This study compared the combination of an AT1 receptor antagonist (irbesartan, IRB) ± a low or a high dose of the NEPi thiorphan in renin-overexpressing, hypertensive TGR(mREN2)27 rats. Methods: TGR(mREN2)27 rats were treated for three weeks with vehicle, IRB (15 mg/kg.day) or IRB + thiorphan (0.1 or 1.0 mg/kg.day; TH0.1 and TH1.0). Hemodynamics were evaluated by telemetry, and vascular reactivity was determined in isolated mesenteric arteries (Mulvany myograph). Results: Baseline mean arterial blood pressure (MAP) was 168±3 mmHg. All treatments lowered MAP by ≈50 mmHg around day 4. After 7 days, MAP started to increase during treatment with IRB or IRB+TH1.0 (to 141±10 mmHg and 133±10 mmHg, respectively, on day 21), while MAP in rats treated with IRB+TH0.1 remained low at 104±5 mmHg on day 21. Heart weight/body weight ratio, cardiac ANP expression and myocyte size decreased only in the IRB+TH0.1 group. Plasma ET1 was increased only by TH1.0 versus IRB alone, and this increase was accompanied by an increase in renal sodium-hydrogen exchanger 3 (NHE3) protein expression: ET1-induced constriction was reduced by IRB+TH0.1 only. Vascular ET B R expression levels and studies with the ET1 type B receptor (ET B R) antagonist BQ788 revealed that this reduction was most likely due to ET B R upregulation. Conclusion: TH0.1 enhanced the blood pressure-lowering effects of irbesartan and diminished cardiac hypertrophy. Higher doses of thiorphan resulted in significant ET1 rises and renal NHE3 upregulation, thereby increasing blood pressure and sodium reabsorption. The simultaneously occurring upregulation of vasodilatory ET B R was insufficient to overcome this effect. Clearly therefore, too much NEPi on top of AT1 receptor antagonism might be harmful.

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Abstract 065: Overexpression of an Intracellular Angiotensin II Fusion Protein Selectively in the Mitochondria of the Proximal Tubules Elevates Blood Pressure in Mice via AT 1a Receptor-mediated Mitochondrial Respiratory and Glycolysis Stress

Hypertension ◽

10.1161/hyp.68.suppl_1.065 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Xiao C Li ◽

Manoocher Soleimani ◽

Hoang Nguyen ◽

Hong Li ◽

Jia L Zhuo

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Fusion Protein ◽

Proximal Tubule ◽

Physiological Role ◽

Proximal Tubules ◽

Ang Ii ◽

Stress Tests ◽

Arterial Blood ◽

Mitochondrial Respiratory

An intracrine mitochondrial renin-angiotensin system (RAS) has recently been identified in various animal and human tissues, but whether the mitochondrial RAS plays a physiological role in the regulation of blood pressure remains unknown. The present study tested whether overexpression of an intracellular angiotensin II fusion protein, ECFP/ANG II, selectively in the mitochondria of the proximal tubules alters blood pressure, and whether the effects may involve AT 1a receptors and the Na + /H + exchanger 3 (NHE3). An adenoviral vector encoding ECFP/ANG II, a mitochondria targeting sequence, and the sglt2 promoter, Ad-sglt2-mito-ECFP/ANG II, was constructed for proximal tubule- and mitochondria-specific overexpression for 2 weeks. In adult male C57BL/6J mice, overexpression of mito-ECFP/ANG II in the mitochondria of the proximal tubules increased systolic blood pressure (SBP) significantly (Control: 116 ± 3 vs. mito-ECFP/ANG II: 128 ± 3 mmHg; p <0.01, n=15). The blood pressure-increasing effect of Ad-sglt2-mito-ECFP/ANG II was blocked in proximal tubule-specific AT 1a -KO mice (Control: 105 ± 2 vs. mito-ECFP/ANG II: 104 ± 4 mmHg; n.s ., n=7), or in proximal tubule-specific NHE3-KO mice (Control: 108 ± 3 vs. mito-ECFP/ANG II: 107 ± 3 mmHg; n.s ., n=13), respectively. In further experiments, mouse proximal tubule cells were transfected with Ad-sglt2-mito-ECFP/ANG II for 48 h and treated with the AT 1 blocker losartan (10 μM) or the AT 2 blocker PD123319 (10 μM) to measure mitochondrial respiratory and glycolytic function using Seahorse XF Cell Mito and XF Glycolysis Stress Tests. The mito-ECFP/ANG II expression was robust and colocalized with MitoTracker® Red FM. Overexpression of mito-ECFP/ANG II markedly increased oxygen consumption rate (OCR) (Control: 139.4 ± 9.2 vs. mito-ECFP/ANG II: 236.3 ± 12.6 pmol/min; p <0.01, n=12) and extracellular acidification rate (ECAR) (Control: 8.8 ± 0.6 vs. mito-ECFP/ANG II: 11.8 ± 1.2 mpH/min; p <0.01, n=12), respectively. Losartan blocked the effects of mito-ECFP/ANG II on OCR and ECAR, whereas PD123319 had no effect. We conclude that intracellular ANG II may activate AT 1 receptors in the mitochondria of the proximal tubules to alter mitochondrial respiratory and glycolytic function and arterial blood pressure.

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P4481NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor prodrug for treating hypertension

European Heart Journal ◽

10.1093/eurheartj/ehz745.0875 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Keck ◽

H De Almeida ◽

D Compere ◽

N Inguimbert ◽

A Flahault ◽

...

Keyword(s):

Blood Pressure ◽

Oral Administration ◽

Sulfonic Acid ◽

Plasma Sodium ◽

High Dose ◽

Hypertensive Rats ◽

Arterial Blood ◽

Angiotensin Iii ◽

Aminopeptidase A ◽

Orally Active

Abstract Background Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We previously showed that aminopeptidase A (APA) generates in the brain, angiotensin III, which exerts a tonic stimulatory control over blood pressure in hypertensive rats. Thus, the central injection of the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), by blocking the formation of brain angiotensin III, normalizes blood pressure in experimental models of hypertension. Therefore, brain APA appears as a potential new therapeutic target for the treatment of hypertension. We then developed RB150/firibastat, a prodrug of EC33, able of inhibiting brain APA activity and decreasing blood pressure in hypertensive rats after oral administration. Purpose However, considering the high dose of orally active RB150/firibastat required to decrease BP in spontaneously hypertensive rats (SHR) (150 mg/kg) and deoxycorticosterone acetate-salt (DOCA-salt) (50 mg/kg) rats, the aim of our work was to develop new more potent APA inhibitor prodrugs with greater bioavailability for inhibiting brain APA activity. Methods We used a salt- and volume-dependent model of hypertension, the DOCA-salt rat. For in vivo assessments of brain APA activity, brains were collected 4 hours after the oral administration. A catheter was inserted into the right femoral artery to monitor mean arterial blood pressure in alert rats. We evaluated plasma arginine-vasopressin (AVP) levels by radioimmunoassay. Rats were individually housed in metabolic cages for urine and electrolyte output measurements. Results We report here the development of a new APA inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929 ((3S,4S)-3-amino-4-mercapto-6-phenyl-hexane-1-sulfonic acid). NI929 is 10 more efficient than EC33 at inhibiting recombinant mouse APA activity in vitro. Following oral administration at a dose of 4 mg/kg in conscious DOCA-salt rats, NI956/QGC006 normalized brain APA activity and induced a marked decrease in blood pressure of −44±13 mmHg four hours after treatment (p<0.001), sustained over ten hours (−21±12 mmHg, p<0.05). Moreover, NI956/QGC006 decreased plasma AVP levels, and increased diuresis and natriuresis, that may decrease blood pressure by reducing the size of the fluid compartment. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations. Conclusions This study shows that NI956/QGC006 is a “best-in-class” central-acting APA inhibitor prodrug, belonging to the same drug class as RB150/firibastat, supporting the strategy of brain APA inhibition for hypertension treatment. Acknowledgement/Funding ANR (Agence Nationale de la Recherche) grant to Catherine Llorens-Cortes (LabCom CARDIOBAPAI) and Quantum Genomics financial support.

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Diuretic response to acute hypertension is blunted during angiotensin II clamp

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00089.2002 ◽

2002 ◽

Vol 283 (4) ◽

pp. R837-R842 ◽

Cited By ~ 19

Author(s):

Patrick K. K. Leong ◽

Yibin Zhang ◽

Li E. Yang ◽

Niels-Henrik Holstein-Rathlou ◽

Alicia A. McDonough

Keyword(s):

Blood Pressure ◽

Urine Output ◽

Tubuloglomerular Feedback ◽

Lithium Clearance ◽

Pressor Effect ◽

Ang Ii ◽

Acute Hypertension ◽

Arterial Blood ◽

Diuretic Response ◽

Hoe 140

Acute hypertension inhibits proximal tubule (PT) fluid reabsorption. The resultant increase in end proximal flow rate provides the error signal to mediate tubuloglomerular feedback autoregulation of renal blood flow and glomerular filtration rate and suppresses renal renin secretion. To test whether the suppression of the renin-angiotensin system during acute hypertension affects the magnitude of the inhibition of PT fluid and sodium reabsorption, plasma ANG II levels were clamped by infusion of the angiotensin-converting enzyme (ACE) inhibitor captopril (12 μg/min) and ANG II after pretreatment with the bradykinin B2 receptor blocker HOE-140 (100 μg/kg bolus). Because ACE also degrades bradykinin, HOE-140 was included to block effect of accumulating vasodilatory bradykinins during captopril infusion. HOE-140 increased the sensitivity of arterial blood pressure to ANG II: after captopril infusion without HOE-140, 20 ng · kg−1 · min−1 ANG II had no pressor effect, whereas with HOE-140, 20 ng · kg−1 · min−1 ANG II increased blood pressure from 104 ± 4 to 140 ± 6 mmHg. ANG II infused at 2 ng · kg−1 · min−1 had no pressor effect after captopril and HOE-140 infusion (“ANG II clamp”). When blood pressure was acutely increased 50–60 mmHg by arterial constriction without ANG II clamp, urine output and endogenous lithium clearance increased 4.0- and 6.7-fold, respectively. With ANG II clamp, the effects of acute hypertension were reduced 50%: urine output and endogenous lithium clearance increased two- and threefold, respectively. We conclude that HOE-140, an inhibitor of the B2 receptor, potentiates the sensitivity of arterial pressure to ANG II and that clamping systemic ANG II levels during acute hypertension blunts the magnitude of the pressure diuretic response.

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Clerodendrum Chinensis Extracts; AeC and EeC Exerts Rapid Antihypertensive Effects in L-NAME Hypertensive Experimental Models

10.1101/2020.07.18.210070 ◽

2020 ◽

Author(s):

Joy I. Odimegwu ◽

Tolulope F. Okanlawon ◽

Obumneme Noel ◽

Ismail Ishola

Keyword(s):

Blood Pressure ◽

Communicable Disease ◽

Scientific Basis ◽

Experimental Models ◽

Dependent Manner ◽

Arterial Blood ◽

High Doses ◽

Mean Differences ◽

Antihypertensive Properties ◽

Dose Dependent

ABSTRACTBackgroundThe rise in occurrence of hypertension, a non-communicable disease and a major factor for chronic renal failure, cardiovascular disease, and stroke, which most times lead to sudden death is worrisome. Resistant hypertension is more common and may have no symptoms at all for months or years, but then can cause heart attack, stroke, and vision and kidney damage. Prevention and quick management of hypertension are therefore essential in reducing the risk of these debilitating ailments. Aqueous and ethanolic extracts of the leaves of Clerodendrum chinensis (AeC and EeC) are used by local communities of West Africa as medicine for rapid antihypertensive actions. We aim to discover the scientific basis for the use of the herb as medicine.MethodsThis work investigates the antihypertensive effects of AeC and EeC in L-Arginine Methyl Ester Hydrochloride (L-NAME)-induced hypertensive rats Acetylcholine, L-Arginine and Sodium Nitroprusside were used as standards. All results were expressed as means ± standard error of mean. Differences were considered significant at p <0.05.ResultsIntravenous administration of the extracts caused a significant decrease in the Mean Arterial Blood Pressure (MABP) in a dose-dependent manner. AeC at 100mg/kg caused a significant decline in blood pressure in a dose-related manner. Likewise at 100mg/kg, EeC reduced MABP steadily from 103.9± 2.55 to 34.1± 0.95mmHg. The two extracts; possess significant antihypertensive properties.ConclusionsBoth extracts show significant antihypertensive effects and at high doses could lead to hypotension and so should be used with care. Further research is necessary to determine safe dosage forms.

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Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea

Journal of Applied Physiology ◽

10.1152/japplphysiol.00696.2020 ◽

2020 ◽

Author(s):

Joshua M. Bock ◽

Brady E. Hanson ◽

Thomas F. Asama ◽

Andrew J. Feider ◽

Satoshi Hanada ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Ventilatory Response ◽

High Dose ◽

Inorganic Nitrate ◽

Obstructive Sleep ◽

Chemoreflex Sensitivity ◽

Nitrate Supplementation ◽

High Doses ◽

Peripheral Chemoreflex

Patients with obstructive sleep apnea (OSA) have increased cardiovascular disease risk largely attributable to hypertension. Heightened peripheral chemoreflex sensitivity (i.e., exaggerated responsiveness to hypoxia) facilitates hypertension in these patients. Nitric oxide blunts the peripheral chemoreflex and patients with OSA have reduced nitric oxide bioavailability. We therefore investigated the dose-dependent effects of acute inorganic nitrate supplementation (beetroot juice), an exogenous nitric oxide source, on blood pressure and cardiopulmonary responses to hypoxia in patients with OSA using a randomized, double-blind, placebo-controlled crossover design. Fourteen patients with OSA (53±10years, 29.2±5.8kg/m2, apnea-hypopnea index=17.8±8.1, 43%F) completed three visits. Resting brachial blood pressure, as well as cardiopulmonary responses to inspiratory hypoxia, were measured before, and two hours after, acute inorganic nitrate supplementation (~0.10mmol [placebo], 4.03mmol [low-dose], and 8.06mmol [high-dose]). Placebo did not increase either plasma [nitrate] (30±52 to 52±23μM, P=0.26) or [nitrite] (266±153 to 277±164nM, P=0.21); however, both increased following low-(29±17 to 175±42μM, 220±137 to 514±352nM) and high-doses (26±11 to 292±90μM, 248±155 to 738±427nM, respectively, P<0.01 for all). Following placebo, systolic blood pressure increased (120±9 to128±10mmHg, P<0.05) whereas no changes were observed following low-(121±11 to 123±8mmHg, P=0.19) or high-dose (124±13 to 124±9mmHg, P=0.96). The peak ventilatory response to hypoxia increased following placebo (3.1±1.2 to 4.4±2.6L/min, P<0.01) but not low-(4.4±2.4 to 5.4±3.4L/min, P=0.11) or high-doses (4.3±2.3 to 4.8±2.7L/min, P=0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time P=0.64). Acute inorganic nitrate supplementation appears to blunt an early-morning rise in systolic blood pressure potentially through suppression of peripheral chemoreflex sensitivity in patients with OSA.

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Angiotensin-(3–4) (Val-Tyr) Normalizes the Elevated Arterial Blood Pressure and Abnormal Na+/Energy Handling Associated With Chronic Undernutrition by Counteracting the Effects Mediated by Type 1 Angiotensin II Receptors

10.21203/rs.3.rs-1149879/v1 ◽

2021 ◽

Author(s):

Amaury Pereira-Acacio ◽

João Veloso-Santos ◽

Luiz Nossar ◽

Gloria Costa-Sarmento ◽

Humberto Muzi-Filho ◽

...

Keyword(s):

Blood Pressure ◽

Proximal Tubule ◽

Energy Intake ◽

Chronic Administration ◽

Poor Quality ◽

Vitamin Supplementation ◽

High Systolic Blood Pressure ◽

Proximal Tubule Cells ◽

Arterial Blood ◽

Control Body

Abstract Purpose To investigate the mechanisms by which chronic administration of a multideficient diet after weaning alters bodily Na+ handling, and culminates in high systolic blood pressure (SBP) at a juvenile age.Methods From 28 to 93 days of age, weaned male Wistar rats were given a diet with low content and poor-quality protein, low lipid, without vitamin supplementation, which mimics the diets consumed in impoverished regions worldwide. We measured food, energy and Na+ ingestion, together with urinary Na+ excretion, Na+ density (Na+ intake/energy intake), plasma Na+ concentration, SBP), and renal proximal tubule Na+-transporting ATPases. Results Undernourished rats aged 93 days had only one-third of the control body mass, lower plasma albumin, higher SBP, higher energy intake, and higher positive Na+ balance accompanied by decreased plasma Na+ concentration. SBP was normalized with Losartan and with Ang-(3–4), and the combination of the 2 substances induced an accentuated negative Na+ balance as a result of strong inhibition of Na+ ingestion. Na+ density in undernourished rats was higher than in control, irrespective of the treatment, and they had downregulated (Na++K+)ATPase and upregulated Na+-ATPase in proximal tubule cells, which returned to control levels after Losartan or Ang-(3–4).Conclusions Na+ density, not only Na+ ingestion, plays a central role in the pathophysiology of elevated SBP in chronically undernourished rats. The observations that Losartan and Ang-(3–4) normalized SBP together with Na+ distribution and handling give support to the proposal that Ang IIÞAT1R and Ang IIÞAT2R axes have opposite roles within the renin-angiotensin-aldosterone system of undernourished juvenile rats.

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Fourier Analysis of Peripheral Blood Pressure and Flow in Intraoperative Assessment of Infrainguinal Arterial Reconstructions

Folia Medica ◽

10.2478/folmed-2014-0015 ◽

2014 ◽

Vol 56 (2) ◽

pp. 102-108

Author(s):

Mihail V. Cheshmedzhiev ◽

Iskra S. Mircheva ◽

Emil D. Jordanov ◽

Nina R. Kovacheva

Keyword(s):

Blood Pressure ◽

Bypass Graft ◽

Volume Flow ◽

Fast Fourier Transformation ◽

Bypass Grafts ◽

Amplitude Ratios ◽

Drug Infusion ◽

Drug Induced ◽

Arterial Blood ◽

Before And After

Abstract AIM: To assess infrainguinal arterial reconstructions by intraoperative flowmetry under the distal anastomosis using a fast Fourier transformation; calculate and compare the amplitude ratios of peripheral arterial blood pressure and volume flow before and after drug-induced vasodilation of occluded bypass grafts and bypass grafts that have been patent at least for 1 year. To find what magnitude of the change of these ratios indicate a long-term patency of the bypass grafting. PATIENTS AND METHODS: We compared the results of the intraoperative flowmetry tests of 97 patients with infrainguinal arterial reconstructions. The patients were divided into two groups based on the graft status: the grafts in 49 patients were patent for at least a year, and 48 patients had failed bypass. We used a fast Fourier transform (FFT) of the pressure and blood flow waves and compared the ratios of their amplitudes before and after administration of a vasodilator drug into the graft. Comparing the ratios obtained before and those after administration of the drug we quantified their change in each group and analysed them. RESULTS: After a drug-induced vasodilation, the blood pressure and flow amplitude ratios for the group with compromised reconstructions were less than 1.9 times smaller than those before drug infusion, while for the group with bypass grafts that had been functional for at least 12 months the ratios declined by more than 1.9≈2 times. CONCLUSION: The magnitude of the change of amplitude ratios of the peripheral pressure and volume flow after drug-induced vasodilation can be used to make an assessment of the bypass graft and the distal arterial segment.

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