Hemorheological parameters in individuals with different levels of oxygen body supply: the effect of nitric oxide and hydrogen sulfi de on erythrocyte microrheological characteristics.

2021 ◽  
Author(s):  
А.В. Муравьев ◽  
П.В. Михайлов ◽  
В.В. Зинчук ◽  
И.А. Тихомирова ◽  
Р.С. Остроумов
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Oxygen Transport ◽  
Blood Viscosity ◽  
Oxygen Supply ◽  
No Donor ◽  
Sodium Hydrosulfide ◽  
Positive Effect ◽  
Different Levels ◽  
Transport Potential

Введение. Доставка кислорода в ткани определяется величиной объемного кровотока; он, в свою очередь, зависит от сосудистых и реологических факторов. Снижение вязкости крови (ВК) может способствовать приросту объемного кровотока и повышению эффективности доставки кислорода. Поскольку ВК тесно связана с микрореологическими свойствами эритроцитов, то можно полагать, что их положительные изменения будут способствовать улучшению кислородтранспортной функции крови. Цель исследования: сравнительный анализ гемореологических профилей у лиц с разным уровнем обеспечения организма кислородом и определение роли оксида азота (NO) и сульфида водорода (H2S) в изменениях микрореологических характеристик эритроцитов. Материалы и методы. На основе результатов определения максимального потребления кислорода (МПК) были сформированы 2 группы, в каждой из которых было по 24 практически здоровых мужчины-добровольца в возрасте от 20 до 35 лет: группа 1 – лица с умеренным обеспечением организма кислородом (МПК = 40–50 мл/кг/мин) и группа 2 – лица с относительно высоким его уровнем (МПК = 51–65 мл/кг/мин). Регистрировали параметры гемореологического профиля, напряжение кислорода в коже предплечья (tсрО2), метаболизм оксида азота (по соотношению нитраты/нитриты, NOx). Для исследования влияния газотрансмиттеров (ГТ) на микрореологию эритроцитов их инкубировали с донором NO (нитропруссидом натрия, 100 мкмоль) и донором H2S (гидросульфидом натрия, 100 мкмоль) с последующей регистрацией деформируемости и агрегации эритроцитов. Результаты. У лиц с относительно высоким обеспечением тканей кислородом отмечалась сниженная вязкость крови, ее высокий кислородтранспортный потенциал, эффективная микрореология эритроцитов и их более высокая чувствительность к ГТ при положительном влиянии последних на агрегацию и деформируемость эритроцитов. Заключение. Данные, полученные на моделях микрореологических ответов эритроцитов на доноры двух газотрансмиттеров, позволяют заключить, что, во-первых, эти ГТ, как сигнальные молекулы, положительно влияют на микрореологические характеристики эритроцитов и, следовательно, на их транспортный потенциал, и, во-вторых, эритроциты лиц, имеющих высокий уровень обеспечения организма кислородом, более чувствительны к регуляторному действию газотрансмиттеров, поскольку их микрореологические ответы на доноры были статистически значимо более выраженными. Background. Oxygen delivery to tissues is determined by the volume of blood flow that, in turn, depends on vascular and rheological factors. Blood viscosity (BV) decreasing can promote an increasing of volumetric blood flow and provide more efficient oxygen transport. Since BV depends on the erythrocyte microrheological properties it can be assumed that their positive changes will contribute to better oxygen transport. Objectives: to investigate hemorheological profiles in individuals with different levels of body oxygen supply and the role of nitrogen oxide (NO) and hydrogen sulfide (H2S) in changes of the erythrocyte microrheological characteristics. Patients/Methods. Based on the determination of maximum oxygen consumption (VO2max), 2 groups were formed, each of which consisted of 24 practically healthy male volunteers aged 20–35 years: group 1 – persons with moderate body oxygen supply (VO2max = 40–50 ml/kg/min) and group 2 – persons with a relatively high body oxygen supply (VO2max = 51–65 ml/kg/min). Hemorheological profi le parameters, oxygen tension in the forearm skin (tcpO2), and nitric oxide metabolism by the ratio of nitrates/nitrites (NOx) were recorded. To study the effect of gasotransmitters (GTs) on erythrocyte microrheology, they were incubated with NO donor (sodium nitroprusside, 100 μmol) and H2S donor (sodium hydrosulfide, 100 μmol), and erythrocytes deformability and aggregation were registered. Results. Individuals with a relatively high oxygen supply of tissues showed a reduced blood viscosity, high blood oxygen transport potential, an effective microrheology of erythrocytes and their higher sensitivity to GTs with their positive effect on erythrocytes aggregation and deformability. Conclusions. The obtained data on models of erythrocyte microrheological responses to donors of two gasotransmitters allow us to conclude that, firstly, these GTs, as signaling molecules, have a positive effect on the erythrocyte microrheological characteristics and, consequently, on their transport potential, and, secondly, erythrocytes from individuals with a high level of oxygen body supply are more sensitive to the regulatory action of GTs, because their microrheological responses to donors were statistically significantly more expressed.

Nitric oxide-induced microvascular permeability alterations: a regulatory role for cGMP

1993 ◽  
Vol 265 (6) ◽  
pp. H1909-H1915 ◽  
Author(s):  
P. Kubes
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Guanylate Cyclase ◽  
Microvascular Permeability ◽  
Independent Effect ◽  
No Donor ◽  
Cyclic Monophosphate ◽  
Protein Clearance ◽  
Guanylate Cyclase Activation ◽  
Permeability Alterations

This study evaluated the physiological effects of compounds that alter guanosine 3',5'-cyclic monophosphate (cGMP) on the increase in vascular protein clearance induced by nitric oxide (NO) synthesis inhibition in the feline small intestine. A lymphatic vessel draining the small bowel was cannulated; vascular protein clearance and intestinal blood flow were measured. N omega-nitro-L-arginine methyl ester (L-NAME), the NO inhibitor, was infused (0.5 mumol/min) into the superior mesenteric artery. Vascular protein clearance increased approximately 4.6-fold, whereas blood flow decreased to 50% of control. Elevation of cGMP by 1) cytosolic guanylate cyclase activation with a NO donor (SIN 1) or 2) a cGMP analogue, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) completely prevented the rise in microvascular permeability associated with L-NAME. Moreover, these compounds reduced (almost 90%) baseline vascular protein clearance, whereas inhibition of cytosolic guanylate cyclase with methylene blue significantly increased this parameter. Atrial natriuretic factor (ANF) has been reported to increase tissue cGMP levels and microvascular permeability. In this study, ANF did indeed increase intestinal microvascular permeability however this occurred independent of changes in intestinal cGMP levels. These data support a role for cGMP associated with NO-induced microvascular permeability alterations and raise the possibility that ANF has a cGMP-independent effect on microvascular permeability within the intestine.

Effects of hematocrit variations on regional hemodynamics and oxygen transport in the dog

1980 ◽  
Vol 238 (4) ◽  
pp. H545-H522 ◽  
Author(s):  
F. C. Fan ◽  
R. Y. Chen ◽  
G. B. Schuessler ◽  
S. Chien
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Blood Vessels ◽  
Oxygen Transport ◽  
Oxygen Supply ◽  
Blood Flows ◽  
Regional Hemodynamics ◽  
Regional Blood Flows ◽  
Splenic Vessels ◽  
The Brain

The responses of alterations in regional hemodynamics and oxygen transport rate to hematocrit (Hct) were studied in 20 pentobarbitalized dogs. Hemodilution was carried out by isovolemic exchange with plasma in 12 dogs and the hemoconcentration with packed cells in 8 dogs. The cardiac output and regional blood flows were determined with the microsphere technique. In hemodilution, the increases of blood flow to the myocardium and the brain were out of proportion to the increase of cardiac output; the oxygen supply to the myocardium remained unchanged while that to the brain decreased only slightly. In hemoconcentration, vasodilation occurred in the myocardium and the brain to maintain constant oxygen supply. Splenic vessels had marked vasoconstriction with Hct alteration in either direction. Blood vessels in the liver, intestine, and kidney responded with a milder vasoconstriction and maintained a constant oxygen supply between Hct of 30-55%. Therefore, during Hct alteration, redistribution of blood flow to myocardium and brain occurred. The optimal Hct range for constant oxygen supply was different among various organs.

Sodium Nitrite Increases Regional Blood Flow in Patients with Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2328-2328
Author(s):  
A. Kyle Mack ◽  
Roberto F. Machado ◽  
Vandana Sachdev ◽  
Mark T. Gladwin ◽  
Gregory J. Kato
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Forearm Blood Flow ◽  
Regional Blood Flow ◽  
Cell Disease ◽  
No Donor ◽  
No Donors ◽  
Before And After

Abstract Patients with sickle cell disease have decreased nitric oxide bioavailability, and studies from several groups have confirmed a blunted response to various NO donors in humans and mice with sickle cell disease. Recently published studies show that nitrite induces vasodilation in humans, apparently mediated by conversion of nitrite to NO. This study is designed to determine the potential therapeutic effect of intra-arterial nitrite infusion to restore nitric oxide dependent blood flow in the forearms of patients with sickle cell disease. Venous occlusion strain gauge plethysmography is used to measure the change of forearm blood flow in patients with sickle cell disease, before and after sequential brachial artery infusions of increasing doses of sodium nitrite. In addition, NO responsiveness before and after nitrite infusion is measured by test doses of the NO donor sodium nitroprusside (SNP). Six patients have completed the study and enrollment is continuing. These data indicate that nitrite promotes regional blood flow in patients with sickle cell disease, albeit with a blunted response compared to our healthy control subjects, in whom we previously have found increased blood flow up to 187% with comparable dosing. The significant but blunted response is consistent with the state of nitric oxide resistance to NO donors that has been seen by several groups in patients and mice with SCD. Additionally, we find in these patients that nitrite partially restores SNP responsiveness, with baseline maximal SNP responses more than doubling on average following nitrite infusion, although this finding is preliminary. No adverse effects of nitrite were seen in these six patients. Our early results support a role for nitrite as an NO donor effective in restoring NO-dependent blood flow in patients with sickle cell disease. Additional translational studies are warranted to evaluate the therapeutic effects of systemic nitrite dosing. Table 1. Forearm Blood Flow Response to Nitrite Infusion Nitrite Dose (micromole/min) Sickle Cell Disease Historical Controls P< .0001 (ANOVA) 0.4 5 +/−7.2% N=6 22 +/−3.2% N=10 4 15 +/− 11% N=6 Not infused 40 49 +/− 8.9% N=6 187 +/− 16%N=18 Table 2. Nitrite Effect on Nitroprusside Responsiveness SNP Dose (micrograms/min) Pre-Nitrite Post-Nitrite P= .02 (RM-ANOVA) N=6 0.8 +21 +/− 5.6% +33 +/− 8.3% 1.6 +15 +/− 5.9% +62 +/− 15.1% 3.2 +29 +/− 6.3% +67 +/− 11.5%

Effects of Nitric Oxide on Blood Flow and Mucociliary Activity in the Human Nose

1998 ◽  
Vol 107 (1) ◽  
pp. 40-46 ◽  
Author(s):  
Thomas Runer ◽  
Sven Lindberg
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Maximum Increase ◽  
No Donor ◽  
Doppler Flowmetry ◽  
Human Nose

In an animal model, nitric oxide (NO) has been shown to increase mucociliary activity in vivo and ciliary beat frequency in vitro. The aim of the present study was to investigate the effects of NO on blood flow and mucociliary activity in the human nose. The concentration of NO in nasal air was measured with a chemiluminescence technique after nebulizing the NO donor sodium nitroprusside (SNP) at a dose of 3.0 mg into the nose in six volunteers, and was found to increase by 50.1% ± 10.0% (mean ± SEM; p <.001) after the SNP challenge. Blood flow measured by laser Doppler flowmetry increased by 67.3% ± 15.5% (p <.05) after challenge with SNP at 1.0 mg, and by 75.4% ± 18.5% at 3.0 mg (p <.01; n = 6). The higher dose, which produced no subjective side effects, was then used in the mucociliary experiments. The maximum increase in nasal mucociliary activity was 57.2% ± 6.7% at 3.0 mg of SNP (n = 5). The findings support the view that NO regulates mucociliary activity and blood flow in the human nasal mucosa.

scholarly journals Hypothesis article: Nitric oxide depletion may aggravate COVID-19 symptoms. 
A new therapy could help

2021 ◽  
Author(s):  
Brecht Daams
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Immune System ◽  
Elderly Patients ◽  
Successful Therapy ◽  
No Donor ◽  
New Therapy ◽  
Kidney Functions ◽  
Positive Results ◽  
Inhaled No

The Corona virus SARS-CoV2 that causes COVID-19 has effects that until now have not been explained. The widespread damage of SARS-CoV2, the comorbidities in critically ill COVID-19 patients, and the symptoms of post-COVID-19 patients show striking similarities with conditions that are related to depletion of nitric oxide (NO) in the human body. Many of the symptoms of the disease may be caused by acute depletion of NO by the immune system. Patients with the highest COVID-19 burden often have comorbidities that are related to chronic depletion of NO. Post-COVID-19 health problems may be caused by earlier depletion of NO. Successful therapy requires sufficient NO levels. Supplementation with NO will increase immunity, help prevent thrombosis, and improve breathing, kidney functions, blood flow and oxygenation in patients, elderly patients and patients with comorbidities in particular. Furthermore, NO helps to prevent SARS-CoV2 from entering the human cell and to suppress viral RNA production. NO is not easy to supplement. A few SARS patients have been treated with inhaled NO with positive results, but inhaled NO can only deliver small quantities of NO. A new therapy has been developed to more effectively supplement NO. It combines the ingestion of nitrates (as NO donor), N-acetylcysteine and vitamin C (promoting NO metabolism) with electrostimulation of the muscles (to trigger the release of NO). It is expected that this therapy can ease the most serious symptoms of (post) COVID-19, especially for elderly and people with comorbidities. A patent has been applied for.

Nitric oxide modulates angiotensin II- and norepinephrine-dependent vasoconstriction in rat kidney

1996 ◽  
Vol 270 (3) ◽  
pp. R630-R635 ◽  
Author(s):  
N. Parekh ◽  
L. Dobrowolski ◽  
A. P. Zou ◽  
M. Steinhausen
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Rat Kidney ◽  
Ang Ii ◽  
No Donor ◽  
Renal Vasoconstriction ◽  
Medullary Blood Flow ◽  
Series Of Experiments ◽  
Synthase Inhibitor

This study compared the vasoconstrictor action of angiotensin II (ANG II) and norepinephrine (NE) with different levels of nitric oxide (NO) in the kidney of anesthetized rats. In one series of experiments, the drugs were infused intravenously, and systemic NO content was reduced by a NO synthase inhibitor, nitro-L-arginine methyl ester (L-NAME). L-NAME significantly enhanced the renal blood flow (RBF) reduction produced by ANG II from 26 to 49%, but it had no significant effect on the change in RBF induced by NE. Medullary blood flow was not influenced by either ANG II or NE given alone or given after L-NAME. In the second series of experiments, all drugs were infused into the renal artery to avoid their systemic and, hence, extrarenal effects. In these experiments, renal content of NO was increased by the NO donor sodium nitroprusside (SNP), decreased by L-NAME, or restored by replacing endogenous NO by exogenous NO (L-NAME + SNP). Effects of both ANG II and NE on RBF were similarly and significantly attenuated by SNP (60% of control), enhanced by L-NAME (200% of control), and restored by L-NAME + SNP (90% of control, not significant). Our results indicate that NO attenuates the renal vasoconstriction due to ANG II or NE and that the antagonism between vasoconstrictors and NO is not due to a constrictor-induced production of NO because exogenous and endogenous NO were equally effective.

Effect of increased whole blood viscosity on regional blood flows in chronically hypoxemic lambs

1994 ◽  
Vol 267 (2) ◽  
pp. H471-H476
Author(s):  
M. Dalinghaus ◽  
H. Knoester ◽  
J. W. Gratama ◽  
J. Van der Meer ◽  
W. G. Zijlstra ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Oxygen Supply ◽  
Arterial Oxygen ◽  
Organ Blood Flow ◽  
Whole Blood Viscosity ◽  
Blood Flows ◽  
Chronic Hypoxemia

In chronic hypoxemia blood flow and oxygen supply to vital organs are maintained, but to nonvital organs they are decreased. We measured organ blood flows (microspheres) and whole blood viscosity in 10 chronically hypoxemic lambs, with an atrial septal defect and pulmonary stenosis, and in 8 control lambs. Vascular hindrance (resistance/viscosity) was calculated to determine to what extent the effect of increased blood viscosity on organ blood flow was compensated for by a decrease in vascular tone. Arterial oxygen saturation was decreased (68 +/- 10 vs. 91 +/- 3%, P < 0.001), and both hemoglobin concentration (145 +/- 10 vs. 109 +/- 9 g/l, P < 0.05) and blood viscosity (4.4 +/- 0.6 vs. 3.6 +/- 0.6 mPa.s, P < 0.05) were increased in hypoxemic lambs. Systemic blood flow, oxygen supply, oxygen uptake, and blood pressures were not significantly different between hypoxemic and control lambs. Myocardial and cerebral blood flow was maintained in hypoxemic lambs, whereas renal, gastrointestinal, splenic, and thyroidal blood flows were at least 30% lower. Vascular hindrance was significantly decreased in the myocardium and tended to be lower in the brain of hypoxemic lambs, but in all other organs it was similar to that in control lambs. It is concluded that blood flow is redistributed in chronic hypoxemia in lambs; myocardial and cerebral blood flow is maintained, whereas blood flow to splanchnic organs, the kidneys, and the thyroids is decreased. The decreased blood flow to organs is a consequence of the increased whole blood viscosity.

Effect of gasotransmitters donors (nitrogen oxide, hydrogen sulfide and carbon monoxide) on erythrocytes microrheological properties

2021 ◽  
Author(s):  
А.В. Муравьев ◽  
И.А. Тихомирова ◽  
Е.П. Петроченко ◽  
Ю.А. Малышева ◽  
Н.В. Кислов
Keyword(s):  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Nitrogen Oxide ◽  
Blood Rheology ◽  
Signaling Molecules ◽  
Target Cells ◽  
No Donor ◽  
Sodium Hydrosulfide ◽  
Total Difference ◽  
Transport Potential

Введение. Микрореологические свойства эритроцитов — их деформируемость и агрегация в значительной степени определяют текучесть цельной крови и ее кислородотранспортный потенциал. При этом эритроциты — это клетки-мишени, на которые действуют сигнальные молекулы. Последние могут регуляторно изменять микромеханические свойства эритроцитов и реологию крови в целом. К сигнальным молекулам относятся и газотрансмиттеры (ГТ) — такие соединения, как оксид азота (NO), сульфид водорода (H2S) и монооксид углерода (CO). Доноры ГТ могут быть основой для разработки лекарственных препаратов для коррекции реологических свойств крови. Цель работы: изучение изменений микрореологических характеристик эритроцитов под влиянием доноров трех газотрансмиттеров — NO, H2S и CO. Материалы и методы. Эритроциты и их восстановленные тени инкубировали с нитропруссидом натрия (НПН, 100 мкмоль) — донором NO, гидросульфидом натрия (NaHS, 100 мкмоль) — донором H2S и трикарбонилхлор (глицинат) рутением (II) (CORM-3, 50 мкмоль) — донором СО. После этого регистрировали деформируемость эритроцитов (ИУЭ), их агрегацию (ПАЭ) и вязкость суспензий (ВС). Результаты. Установлено, что под влиянием всех трех доноров ГТ происходят заметные изменения микрореологических характеристик эритроцитов и их теней (в среднем на 13–16%; p < 0,05). Важно заметить, что сдвиги ИУЭ, ПАЭ и ВС под влиянием доноров газотрансмиттеров были сходными по величине, и суммарная разница их микрореологических эффектов на три разных донора ГТ не превышала 3%. Заключение. На основании полученных данных и их анализа можно заключить, что эритроциты качественно и количественно примерно одинаково отвечают на действие трех разных доноров ГТ положительными изменениями их микрореологических характеристик и особенно агрегации, которая снижалась более чем на 30%. Background. Erythrocytes microrheological properties (deformability and aggregation) largely determine the fluidity of whole blood and its oxygen transport potential. At the same time erythrocytes are target cells for signaling molecules acting. The latter can regulate erythrocytes micromechanical properties and blood rheology in general. Signaling molecules also include gasotransmitters (GT) — compounds such as nitrogen oxide (NO), hydrogen sulfide (H2S) and carbon monoxide (CO). GT donors can form the basis of drugs for blood rheology correction. Objectives: to study the changes of erythrocytes microrheological characteristics under the influence of donors of three gasotransmitters — NO, H2S and CO. Materials/Methods. Erythrocytes and their restored shadows were incubated with sodium nitroprusside (SNP, 100 μmol) — NO donor, sodium hydrosulfide (NaHS, 100 μmol) — H2S donor, and with tricarbonylchlor (glycinate) ruthenium (II) (CORM-3, 50 μmol) — CO donor. Thereafter we registered erythrocytes deformability (ED), their aggregation (EA) and suspensions viscosity (SV). Results. All three GT donors noticeably changed microrheological characteristics of erythrocytes and their shadows (on average by 13–16%; p < 0.05). It’s important that the shifts of ED, EA, and SV under the influence of gasotransmitter donors were similar in magnitude, and the total difference in their microrheological effects on three different GT donors did not exceed 3%. Conclusions. Erythrocytes qualitatively and quantitatively approximately equally responded to the action of three different GT donors by positive changes in their microrheological characteristics and especially by aggregation that decreased by more than 30%.

A perinatal nitric oxide donor increases renal vascular resistance and ameliorates hypertension and glomerular injury in adult fawn-hooded hypertensive rats

2008 ◽  
Vol 294 (6) ◽  
pp. R1847-R1855 ◽  
Author(s):  
Maarten P. Koeners ◽  
Branko Braam ◽  
Dionne M. van der Giezen ◽  
Roel Goldschmeding ◽  
Jaap A. Joles
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Vascular Resistance ◽  
Renal Injury ◽  
Renal Vascular Resistance ◽  
Perinatal Exposure ◽  
Hypertensive Rats ◽  
No Donor ◽  
Renal Vascular

Enhancing perinatal nitric oxide (NO) availability persistently reduces blood pressure in spontaneously hypertensive rats. We hypothesize that this approach can be generalized to other models of genetic hypertension, for instance those associated with renal injury. Perinatal exposure to the NO donor molsidomine was studied in fawn-hooded hypertensive (FHH) rats, a model of mild hypertension, impaired preglomerular resistance, and progressive renal injury. Perinatal molsidomine increased urinary NO metabolite excretion at 8 wk of age, i.e., 4 wk after treatment was stopped ( P < 0.05). Systolic blood pressure was persistently reduced after molsidomine (42-wk females: 118 ± 3 vs. 141 ± 5 and 36-wk males: 139 ± 4 vs. 158 ± 4 mmHg; both P < 0.001). Perinatal treatment decreased glomerular filtration rate ( P < 0.05) and renal blood flow ( P < 0.01) and increased renal vascular resistance ( P < 0.05), without affecting filtration fraction, suggesting persistently increased preglomerular resistance. At 4 wk of age natriuresis was transiently increased by molsidomine ( P < 0.05). Molsidomine decreased glomerulosclerosis ( P < 0.05). Renal blood flow correlated positively with glomerulosclerosis in control ( P < 0.001) but not in perinatally treated FHH rats. NO dependency of renal vascular resistance was increased by perinatal molsidomine. Perinatal enhancement of NO availability can ameliorate development of hypertension and renal injury in FHH rats. Paradoxically, glomerular protection by perinatal exposure to the NO donor molsidomine may be due to persistently increased preglomerular resistance. The mechanisms by which increased perinatal NO availability can persistently reprogram kidney function and ameliorate hypertension deserve further study.

Sign in / Sign up

Export Citation Format

Share Document