Role of renal NO production in the regulation of medullary blood flow

2003 ◽  
Vol 284 (6) ◽  
pp. R1355-R1369 ◽  
Author(s):  
Allen W. Cowley ◽  
Takefumi Mori ◽  
David Mattson ◽  
Ai-Ping Zou

The unique role of nitric oxide (NO) in the regulation of renal medullary function is supported by the evidence summarized in this review. The impact of reduced production of NO within the renal medulla on the delivery of blood to the medulla and on the long-term regulation of sodium excretion and blood pressure is described. It is evident that medullary NO production serves as an important counterregulatory factor to buffer vasoconstrictor hormone-induced reduction of medullary blood flow and tissue oxygen levels. When NO synthase (NOS) activity is reduced within the renal medulla, either pharmacologically or genetically [Dahl salt-sensitive (S) rats], a super sensitivity to vasoconstrictors develops with ensuing hypertension. Reduced NO production may also result from reduced cellular uptake of l-arginine in the medullary tissue, resulting in hypertension. It is concluded that NO production in the renal medulla plays a very important role in sodium and water homeostasis and the long-term control of arterial pressure.

1999 ◽  
Vol 276 (3) ◽  
pp. R790-R798 ◽  
Author(s):  
Ai-Ping Zou ◽  
Kasem Nithipatikom ◽  
Pin-Lan Li ◽  
Allen W. Cowley

This study determined the levels of adenosine in the renal medullary interstitium using microdialysis and fluorescence HPLC techniques and examined the role of endogenous adenosine in the control of medullary blood flow and sodium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowmetry. Analysis of microdialyzed samples showed that the adenosine concentration in the renal medullary interstitial dialysate averaged 212 ± 5.2 nM, which was significantly higher than 55.6 ± 5.3 nM in the renal cortex ( n = 9). Renal medullary interstitial infusion of a selective A1antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol ⋅ kg−1 ⋅ min−1, n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A2 receptor blocker 3,7-dimethyl-1-propargylxanthine (DMPX; 150 pmol ⋅ kg−1 ⋅ min−1, n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal medullary interstitial infusion of adenosine produced a dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses from 3 to 300 pmol ⋅ kg−1 ⋅ min−1( n = 7). These effects of adenosine were markedly attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a selective A3receptor agonist, N 6-benzyl-5′-( N-ethylcarbonxamido)adenosine (300 pmol ⋅ kg−1 ⋅ min−1, n = 6) into the renal medulla had no effect on medullary blood flows or renal function. Glomerular filtration rate and arterial pressure were not changed by medullary infusion of any drugs. Our results indicate that endogenous medullary adenosine at physiological concentrations serves to dilate medullary vessels via A2 receptors, resulting in a natriuretic response that overrides the tubular A1 receptor-mediated antinatriuretic effects.


1998 ◽  
Vol 275 (5) ◽  
pp. R1667-R1673 ◽  
Author(s):  
Noriyuki Miyata ◽  
Ai Ping Zou ◽  
David L. Mattson ◽  
Allen W. Cowley

Studies were designed to examine the effects of renal medullary interstitial infusion of l-arginine (l-Arg) on the development of high-salt-induced hypertension in Dahl salt-sensitive/Rapp (DS) rats. The threshold dose of l-Arg (300 μg ⋅ kg−1 ⋅ min−1) that increased the renal medullary blood flow without altering the cortical blood flow was first determined in anesthetized DS rats. Studies were then carried out to determine the effects of this dose ofl-Arg on salt-induced hypertension in DS rats. In the absence of chronic medullaryl-Arg infusion, mean arterial pressure (MAP) increased in DS rats from 125 ± 2 to 167 ± 5 mmHg by day 5 of a high-salt diet (4.0%), with no change observed in Wistar-Kyoto (WKY) or Dahl salt-resistant/Rapp (DR) rats. MAP did not change significantly with medullary infusion ofl-Arg alone in DR rats (control = 104 ± 1 mmHg) or in WKY rats (control = 120 ± 3 mmHg) and was not significantly changed from these levels during the 7 days ofl-Arg infusion combined with high-NaCl diet. The same amount of l-Arg that prevented salt-induced hypertension in DS rats when infused into the renal medulla (300 μg ⋅ kg−1 ⋅ min−1) failed to blunt salt-induced hypertension when administered intravenously to DS rats. DS rats receiving l-Arg (300 μg ⋅ kg−1 ⋅ min−1iv) exhibited an increase in plasma l-Arg from control concentrations of 138 ± 11 to 218 ± 4 μmol/l, while MAP, which averaged 124 ± 3 mmHg during the 3-day control period, rose to 165 ± 5 mmHg by day 5of high salt (4%) intake. These results indicate that the prevention of salt sensitivity in DS rats was due specifically to the action of l-Arg on renal medullary function and that DS rats may have a deficit of medullary substrate availability and NO production.


2003 ◽  
Vol 284 (1) ◽  
pp. R13-R27 ◽  
Author(s):  
David L. Mattson

The control of renal medullary perfusion and the impact of alterations in medullary blood flow on renal function have been topics of research interest for almost four decades. Many studies have examined the vascular architecture of the renal medulla, the factors that regulate renal medullary blood flow, and the influence of medullary perfusion on sodium and water excretion and arterial pressure. Despite these studies, there are still a number of important unanswered questions in regard to the control of medullary perfusion and the influence of medullary blood flow on renal excretory function and blood pressure. This review will first address the vascular architecture of the renal medulla and the potential mechanisms whereby medullary perfusion may be regulated. The known extrarenal and local systems that influence the medullary vasculature will then be summarized. Finally, this review will present an overview of the evidence supporting the concept that selective changes in medullary perfusion can have a potent influence on sodium and water excretion with a long-term influence on arterial blood pressure regulation.


1988 ◽  
Vol 254 (3) ◽  
pp. F417-F424 ◽  
Author(s):  
W. A. Cupples ◽  
T. Sakai ◽  
D. J. Marsh

Angiotensin II has been implicated in the regulation of medullary blood flow and is known to interact with prostaglandins at sites within the kidney. Therefore the role of angiotensin in control of vasa recta blood flow was studied in antidiuretic, Munich-Wistar rats. We also tested the hypothesis that prostaglandins act to modulate the effect of angiotensin. Total renal blood flow was measured by an electromagnetic flow probe, vasa recta blood flow by a dual-slit method. Captopril was used to confirm that angiotensin blockade increased renal blood flow (by 15 +/- 4%). Captopril and saralasin were used to show that angiotensin blockade increased vasa recta blood flow (by 23 +/- 9 and 14 +/- 7%, respectively). The results demonstrate a tonic constrictor effect of angiotensin in the renal medulla. Exogenous angiotensin II, delivered intravenously, failed to mimic the effect of endogenous angiotensin. Indomethacin did not alter blood pressure or renal blood flow but did reduce vasa recta blood flow by 20 +/- 3%, suggesting that prostaglandins act preferentially on the medullary circulation. Nor did it alter the response of blood pressure, of renal blood flow, or of vasa recta blood flow to captopril. Moreover, prior angiotensin blockade with either captopril or saralasin enhanced the medullary vasoconstrictor effect of indomethacin (P less than 0.05). These results are not consistent with the hypothesis that prostaglandins act primarily as angiotensin modulators. They suggest that the medullary interaction between angiotensin and prostaglandins differs from that in the cortex.


Author(s):  
Giuseppe Lisco ◽  
Vito A. Giagulli ◽  
Giovanni De Pergola ◽  
Anna De Tullio ◽  
Edoardo Guastamacchia ◽  
...  

Background: The novel pandemic of Coronavirus disease 2019 (COVID-19) has becoming a public health issue since March 2020 considering that more than 30 million people were found to be infected worldwide. Particularly, recent evidences suggested that men may be considered as at higher risk of poor prognosis or death once the infection occurred and concerns surfaced in regard of the risk of a possible testicular injury due to SARS-CoV-2 infection. Results: Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, younger man with normal testicular function compared to women of similar age are prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that SARS-CoV-2 genome is not normally found in gonads and gametes, therefore sex transmission could be excluded as a possible way to spread the COVID-19. Conclusion: Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection even in case it occurred asymptomatically but no long-term evidences are currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
David Western ◽  
Victor N. Mose ◽  
David Maitumo ◽  
Caroline Mburu

Abstract Background Studies of the African savannas have used national parks to test ecological theories of natural ecosystems, including equilibrium, non-equilibrium, complex adaptive systems, and the role of top-down and bottom-up physical and biotic forces. Most such studies have excluded the impact of pastoralists in shaping grassland ecosystems and, over the last half century, the growing human impact on the world’s rangelands. The mounting human impact calls for selecting indicators and integrated monitoring methods able to track ecosystem changes and the role of natural and human agencies. Our study draws on five decades of monitoring the Amboseli landscape in southern Kenya to document the declining role of natural agencies in shaping plant ecology with rising human impact. Results We show that plant diversity and productivity have declined, biomass turnover has increased in response to a downsizing of mean plant size, and that ecological resilience has declined with the rising probability of extreme shortfalls in pasture production. The signature of rainfall and physical agencies in driving ecosystem properties has decreased sharply with growing human impact. We compare the Amboseli findings to the long-term studies of Kruger and Serengeti national parks to show that the human influence, whether by design or default, is increasingly shaping the ecology of savanna ecosystems. We look at the findings in the larger perspective of human impact on African grasslands and the world rangelands, in general, and discuss the implications for ecosystem theory and conservation policy and management. Conclusions The Amboseli study shows the value of using long-term integrated ecological monitoring to track the spatial and temporal changes in the species composition, structure, and function of rangeland ecosystems and the role of natural and human agencies in the process of change. The study echoes the widespread changes underway across African savannas and world’s rangelands, concluding that some level of ecosystem management is needed to prevent land degradation and the erosion of ecological function, services, and resilience. Despite the weak application of ecological theory to conservation management, a plant trait-based approach is shown to be useful in explaining the macroecological changes underway.


2021 ◽  
pp. 003329412110051
Author(s):  
Rashmi Gupta ◽  
Jemima Jacob ◽  
Gaurav Bansal

Psychosocial stressors and social disadvantages contribute to inequalities in opportunities and outcomes. In the current paper, we use an epidemiological perspective and highlight the role stress plays on individuals by reviewing the outcomes of major stressors such as poverty and unemployment. We further analyzed the psychological and physical cost of these stressors and their long-term impact. We examined the role of universal basic income and closely looked at income experiments that were implemented in the past, in terms of their effectiveness in enhancing the community as well as individual outcomes and propose the UBI as a tool for alleviating the impact of these stressors. At a time when a major pandemic (e.g., COVID-19) threatens economic stability and health globally, we believe the UBI is relevant now, more than ever.


2005 ◽  
Vol 289 (6) ◽  
pp. F1324-F1332 ◽  
Author(s):  
Manish M. Tiwari ◽  
Robert W. Brock ◽  
Judit K. Megyesi ◽  
Gur P. Kaushal ◽  
Philip R. Mayeux

Acute renal failure (ARF) is a frequent and serious complication of endotoxemia caused by lipopolysaccharide (LPS) and contributes significantly to mortality. The present studies were undertaken to examine the roles of nitric oxide (NO) and caspase activation on renal peritubular blood flow and apoptosis in a murine model of LPS-induced ARF. Male C57BL/6 mice treated with LPS ( Escherichia coli) at a dose of 10 mg/kg developed ARF at 18 h. Renal failure was associated with a significant decrease in peritubular capillary perfusion. Vessels with no flow increased from 7 ± 3% in the saline group to 30 ± 4% in the LPS group ( P < 0.01). Both the inducible NO synthase inhibitor l- N6-1-iminoethyl-lysine (l-NIL) and the nonselective caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD) prevented renal failure and reversed perfusion deficits. Renal failure was also associated with an increase in renal caspase-3 activity and an increase in renal apoptosis. Both l-NIL and Z-VAD prevented these changes. LPS caused an increase in NO production that was blocked by l-NIL but not by Z-VAD. Taken together, these data suggest NO-mediated activation of renal caspases and the resulting disruption in peritubular blood flow are an important mechanism of LPS-induced ARF.


2021 ◽  
Vol 30 (1) ◽  
pp. 181-203
Author(s):  
Tal Braverman-Uriel ◽  
Tal Litvak-Hirsch

The impact of sexuality on mental wellbeing in women in long-term relationships has only been partially investigated. Emphasis has been on quantitative research studies that do not capture the breadth of the field. The present study looked at how and to what extent women maintain sexual desire in long-term relationships, and how sexuality affects their mental wellbeing. The study used a qualitative narrative approach and included semi-structured interviews with approximately 20 Israeli women aged 40–55 from similar socioeconomic backgrounds and in longstanding, permanent relationships. The findings indicate significant development over the years in the perception of the role of sexuality and its impact on mental wellbeing. The path to good sexuality can and should follow women’s leadership and initiative. Such women have the desire to make an impact, willingness to make an effort, and even an actual ability to exert influence. The interviewees’ tools, strategies, insights and ways of coping can serve as models for other women seeking better sexuality in a long-term relationship.


2001 ◽  
Vol 280 (1) ◽  
pp. H327-H333 ◽  
Author(s):  
Laurent P. Audoly ◽  
Xiaoping Ruan ◽  
Victoria A. Wagner ◽  
Jennifer L. Goulet ◽  
Stephen L. Tilley ◽  
...  

The kidney plays a central role in long-term regulation of arterial blood pressure and salt and water homeostasis. This is achieved in part by the local actions of paracrine and autacoid mediators such as the arachidonic acid-prostanoid system. The present study tested the role of specific PGE2 E-prostanoid (EP) receptors in the regulation of renal hemodynamics and vascular reactivity to PGE2. Specifically, we determined the extent to which the EP2 and EP3 receptor subtypes mediate the actions of PGE2 on renal vascular tone. Renal blood flow (RBF) was measured by ultrasonic flowmetry, whereas vasoactive agents were injected directly into the renal artery of male mice. Studies were performed on two independent mouse lines lacking either EP2or EP3 (−/−) receptors and the results were compared with wild-type controls (+/+). Our results do not support a unique role of the EP2 receptor in regulating overall renal hemodynamics. Baseline renal hemodynamics in EP2−/− mice [RBF EP2−/−: 5.3 ± 0.8 ml · min−1 · 100 g kidney wt−1; renal vascular resistance (RVR) 19.7 ± 3.6 mmHg · ml−1 · min · g kidney wt] did not differ statistically from control mice (RBF +/+: 4.0 ± 0.5 ml · min−1 · 100 g kidney wt−1; RVR +/+: 25.4 ± 4.9 mmHg · ml−1 · min · 100 g kidney wt−1). This was also the case for the peak RBF increase after local PGE2 (500 ng) injection into the renal artery (EP2−/−: 116 ± 4 vs. +/+: 112 ± 2% baseline RBF). In contrast, we found that the absence of EP3receptors in EP3−/− mice caused a significant increase (43%) in basal RBF (7.9 ± 0.8 ml · min−1 · g kidney wt−1, P < 0.05 vs. +/+) and a significant decrease (41%) in resting RVR (11.6 ± 1.4 mmHg · ml−1 · min · g kidney wt−1, P < 0.05 vs. +/+). Local administration of 500 ng of PGE2 into the renal artery caused more pronounced renal vasodilation in EP3−/− mice (128 ± 2% of basal RBF, P < 0.05 vs. +/+). We conclude that EP3 receptors mediate vasoconstriction in the kidney of male mice and its actions are tonically active in the basal state. Furthermore, EP3receptors are capable of buffering PGE2-mediated renal vasodilation.


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