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.

scholarly journals Progressive dysfunction of nitric oxide synthase in a lamb model of chronically increased pulmonary blood flow: a role for oxidative stress

2008 ◽  
Vol 295 (5) ◽  
pp. L756-L766 ◽  
Author(s):  
Peter E. Oishi ◽  
Dean A. Wiseman ◽  
Shruti Sharma ◽  
Sanjiv Kumar ◽  
Yali Hou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Lung Tissue ◽  
Pulmonary Blood Flow ◽  
Artery Pressure ◽  
Oxide Synthase ◽  
Inhaled No

Cardiac defects associated with increased pulmonary blood flow result in pulmonary vascular dysfunction that may relate to a decrease in bioavailable nitric oxide (NO). An 8-mm graft (shunt) was placed between the aorta and pulmonary artery in 30 late gestation fetal lambs; 27 fetal lambs underwent a sham procedure. Hemodynamic responses to ACh (1 μg/kg) and inhaled NO (40 ppm) were assessed at 2, 4, and 8 wk of age. Lung tissue nitric oxide synthase (NOS) activity, endothelial NOS (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), and heat shock protein 90 (HSP90), lung tissue and plasma nitrate and nitrite (NOx), and lung tissue superoxide anion and nitrated eNOS levels were determined. In shunted lambs, ACh decreased pulmonary artery pressure at 2 wk ( P < 0.05) but not at 4 and 8 wk. Inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). In control lambs, ACh and inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). Total NOS activity did not change from 2 to 8 wk in control lambs but increased in shunted lambs (ANOVA, P < 0.05). Conversely, NOxlevels relative to NOS activity were lower in shunted lambs than controls at 4 and 8 wk ( P < 0.05). eNOS protein levels were greater in shunted lambs than controls at 4 wk of age ( P < 0.05). Superoxide levels increased from 2 to 8 wk in control and shunted lambs (ANOVA, P < 0.05) and were greater in shunted lambs than controls at all ages ( P < 0.05). Nitrated eNOS levels were greater in shunted lambs than controls at each age ( P < 0.05). We conclude that increased pulmonary blood flow results in progressive impairment of basal and agonist-induced NOS function, in part secondary to oxidative stress that decreases bioavailable NO.

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.

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&lt; .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.

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.

scholarly journals Altered reactivity and nitric oxide signaling in the isolated thoracic duct from an ovine model of congenital heart disease with increased pulmonary blood flow

2014 ◽  
Vol 306 (7) ◽  
pp. H954-H962 ◽  
Author(s):  
Sanjeev A. Datar ◽  
Peter E. Oishi ◽  
Wenhui Gong ◽  
Stephen H. Bennett ◽  
Christine E. Sun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Thoracic Duct ◽  
Pulmonary Blood Flow ◽  
Fold Increase ◽  
Lymph Flow ◽  
Nitric Oxide Signaling ◽  
Tension Properties ◽  
Cgmp Signaling ◽  
Inhaled No

We have previously shown decreased pulmonary lymph flow in our lamb model of chronically increased pulmonary blood flow, created by the in utero placement of an 8-mm aortopulmonary shunt. The purpose of this study was to test the hypothesis that abnormal lymphatic function in shunt lambs is due to impaired lymphatic endothelial nitric oxide (NO)-cGMP signaling resulting in increased lymphatic vascular constriction and/or impaired relaxation. Thoracic duct rings were isolated from 4-wk-old shunt ( n = 7) and normal ( n = 7) lambs to determine length-tension properties, vascular reactivity, and endothelial NO synthase protein. At baseline, shunt thoracic duct rings had 2.6-fold higher peak to peak tension and a 2-fold increase in the strength of contractions compared with normal rings ( P < 0.05). In response to norepinephrine, shunt thoracic duct rings had a 2.4-fold increase in vascular tone compared with normal rings ( P < 0.05) and impaired relaxation in response to the endothelium-dependent dilator acetylcholine (63% vs. 13%, P < 0.05). In vivo, inhaled NO (40 ppm) increased pulmonary lymph flow (normalized for resistance) ∼1.5-fold in both normal and shunt lambs ( P < 0.05). Inhaled NO exposure increased bioavailable NO [nitrite/nitrate (NO x); ∼2.5-fold in normal lambs and ∼3.4-fold in shunt lambs] and cGMP (∼2.5-fold in both) in the pulmonary lymph effluent ( P < 0.05). Chronic exposure to increased pulmonary blood flow is associated with pulmonary lymphatic endothelial injury that disrupts NO-cGMP signaling, leading to increased resting vasoconstriction, increased maximal strength of contraction, and impaired endothelium-dependent relaxation. Inhaled NO increases pulmonary lymph NO x and cGMP levels and pulmonary lymph flow in normal and shunt lambs. Therapies that augment NO-cGMP signaling within the lymphatic system may provide benefits, warranting further study.

scholarly journals Immunity Correction by a Foot Method of the Body Systemic Mobilization

2021 ◽  
Vol 20 (5) ◽  
pp. 53-64
Author(s):  
Ramil R. Amerkhanov ◽  
Radislav R. Amerkhanov
Keyword(s):  
Blood Flow ◽  
Immune System ◽  
Human Body ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Lymph Flow ◽  
The Body ◽  
Age Group ◽  
The Third ◽  
Positive Results

Physical rehabilitation, by the foot method of body systemic mobilization, is a new medical technology. In connection with the current global unstable infectious situation, the need arose again to return to the question of finding and developing a systematic approach of simple and generally available physical methods. Aim. Analyze and evaluate the effect of the method of systemic mobilization of the body with the foot on the immune system of the human body, in order to prevent and rehabilitate post-infectious conditions. Material and methods. The research was carried out in various climatic zones. The procedures were based on the techniques of the first, second and third orders, in the second and third age groups. The first group consisted of patients of the second age group (13-60 years old). The second study group was represented by the third age group (60 years +). Materials of the first age group (up to 13 years old) were not submitted to the analysis. The method of exposure stipulated only the canonical motion direction in the selected sessions, the session lasted within 40-70 minutes, every day, for 10-30 days, taking into account weight, age and chronic diseases. 237 male and female patients’ material was reviewed and analyzed. Results and discussion. The method of systemic mobilization of the body exposed to the foot showed more significant positive results in the second age group - 92.8% and less in the third – 78.6% . To achieve positive results, it took more procedures 4 ± 1.0 in a humid climate compared to a dry one. It has been approved that accelerated blood flow in the main and collateral vessels triggers the activity of the lymphatic system. In the primary lymphoid organs, the hematopoietic function is restored and increased, optimizing lymphopoiesis and the state of lymphodynamics. Techniques of the first order (level) restore the flow of lymph through the superficial lymphatic vessels, collecting and producing outflow of lymph from the skin, subcutaneous tissue, superficial fascia and the surface layer of muscle fibers.Techniques of the second order (level) affect the lymph flow of deep lymphatic vessels, collecting lymph from muscles, joints and bones, producing outflow from deeply located tissues, lymphatic vessels lying along the arteries and veins of the same name, actively anastomosing with a network of superficial lymphatic vessels. Techniques of the III order (level) promote lymph flow through the lymphatic capillaries, from intra- and extra-organ lymphatic vessels, trunks and ducts. These techniques create conditions for accelerating drainage in the thoracic duct, producing an “emptying” effect by a direct physical coercion on the vertebral column, penetrating deeply. Conclusion. This method has statistically confirmed studies that indicate its ability to significantly increase the speed of blood flow in the main and adjacent vessels. The method can be considered as having a positive effect on lymphodynamics, in particular on lymphatic capillaries emanating from intra- and extra organ lymphatic vessels, trunks and ducts. By increasing the transport function of the lymphatic vessels, providing a full blood supply (nutrition) to the primary organs of the lymphatic system, exerting a stimulating effect on the spirally oriented lymphangion myocytes, in a soft and carefully worked out way, the foot method of systemic body mobilization creates optimal conditions for the correction of the immune system. Thus, it is able to protect the internal environment of the human body from foreign agents.

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.

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.

Intracoronary nitric oxide improves postischemic coronary blood flow and myocardial contractile function

1995 ◽  
Vol 269 (3) ◽  
pp. H1113-H1121 ◽  
Author(s):  
R. Pabla ◽  
A. J. Buda ◽  
D. M. Flynn ◽  
D. B. Salzberg ◽  
D. J. Lefer
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Neutrophil Infiltration ◽  
Myeloperoxidase Activity ◽  
No Donor ◽  
Saline Vehicle

In the present study a novel nitric oxide (NO) donor, CAS-1609, was utilized as a means of coronary NO replenishment in a canine model of myocardial ischemia-reperfusion. Administration of CAS-1609 (1.25 mg iv) 10 min before reperfusion, followed by a 1 mg/h intracoronary infusion throughout the 4.5-h reperfusion period, resulted in significant improvement in postischemic transmural myocardial blood flow (0.66 +/- 0.09 vs. 0.37 +/- 0.08 ml.min-1.g-1 for saline vehicle, P < 0.05). Dogs receiving NO supplementation also exhibited a significant recovery of myocardial contractility after 4.5 h of reperfusion (30 +/- 2% area ejection fraction vs. 22 +/- 2% for saline vehicle, P < 0.05). Moreover, myocardial necrosis as a percentage of the area at risk was reduced from 28.9 +/- 4.3% in the saline group to 8.5 +/- 2.6% in the CAS-1609 group (P < 0.01), while ischemic zone myeloperoxidase activity, indicative of neutrophil infiltration, was also attenuated by 70% with NO therapy. Injection of acetylcholine and nitroglycerin into the left circumflex coronary artery revealed a significant impairment of vasodilator responses in the saline vehicle dogs at 2 h of reperfusion. However, dogs treated with the NO donor demonstrated postischemic vasodilator responses which were similar to baseline (P = not significant vs. baseline). These studies demonstrate that intracoronary administration of NO significantly augments postischemic coronary blood flow and contractile function following ischemia and reperfusion. In addition, NO therapy reduces coronary vascular injury, attenuates myocardial necrosis, and reduces neutrophil infiltration. The cardioprotective actions of intracoronary NO administration may be related to the potent antineutrophil actions of NO.

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