Nitric oxide mediates collecting duct endothelin‐1 effects on blood pressure

Atrial natriuretic peptide (ANP), via its guanylyl cyclase (GC)-A receptor, plays a key role in the regulation of arterial blood pressure (ABP) and volume. Endothelial-restricted deletion of GC-A in mice [endothelial cell (EC) GC-A knockout (KO)] resulted in hypervolemic hypertension, demonstrating that the endothelium participates in the hypotensive and hypovolemic actions of ANP. Published studies showed that ANP modulates the release of the vasoactive factors nitric oxide (NO) and endothelin-1 (ET-1) from cultured endothelia. Based on these observations, we examined the role of these endothelial factors in ANP-dependent vasodilatation (studied in isolated arteries) and chronic regulation of ABP (measured in awake mice by tail-cuff plethysmography). ANP induced concentration-dependent vasorelaxations of aortic, carotid, and pulmonary arteries. These responses were not different between control and EC GC-A KO mice, and were significantly enhanced after inhibition of NO synthase [by N(G)-nitro-l-arginine-methyl ester]. Intravenous administration of N(G)-nitro-l-arginine-methyl ester to conscious mice significantly increased ABP. The extent of these hypertensive reactions was similar in EC GC-A KO mice and control littermates (increases in systolic blood pressure by ∼25 mm Hg). Conversely, antagonism of ET-1/endothelin-A receptors with BQ-123 reduced ABP significantly and comparably in both genotypes (by ∼11 mm Hg). Finally, the vascular and tissue expression levels of components of the NO system and of immunoreactive ET-1 were not different in control and EC GC-A KO mice. We conclude that the endothelium, but not modulation of endothelial NO or ET-1, participates in the chronic regulation of ABP by ANP.

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Role of prostaglandins in collecting duct-derived endothelin-1 regulation of blood pressure and water excretion

AJP Renal Physiology ◽

10.1152/ajprenal.00307.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. F1805-F1810 ◽

Cited By ~ 18

Author(s):

Yuqiang Ge ◽

Kevin A. Strait ◽

Peter K. Stricklett ◽

Tianxin Yang ◽

Donald E. Kohan

Keyword(s):

Blood Pressure ◽

Collecting Duct ◽

Urine Volume ◽

Mrna Levels ◽

Water Excretion ◽

Salt Loading ◽

Endothelin 1 ◽

Cox 2 ◽

Cox 1

Collecting duct (CD)-derived endothelin-1 (ET-1) exerts natriuretic, diuretic, and hypotensive effects. In vitro studies have implicated cyclooxygenase (COX) metabolites, and particularly PGE2, as important mediators of CD ET-1 effects. However, it is unknown whether PGE2 mediates CD-derived ET-1 actions in vivo. To test this, CD ET-1 knockout (KO) and control mice were studied. During normal salt and water intake, urinary PGE2 excretion was unexpectedly increased in CD ET-1 KO mice compared with controls. Salt loading markedly increased urinary PGE2 excretion in both groups of mice; however, the levels remained relatively higher in KO animals. Acutely isolated inner medullary collecting duct (IMCD) from KO mice also had increased PGE2 production. The increased IMCD PGE2 was COX-2 dependent, since NS-398 blocked all PGE2 production. However, increased CD ET-1 KO COX-2 protein or mRNA could not be detected in inner medulla or IMCD, respectively. Inner medullary COX-1 mRNA and protein levels and IMCD COX-1 mRNA levels were unaffected by Na intake or CD ET-1 KO. KO mice on a normal or high-Na diet had elevated blood pressure compared with controls; this difference was not altered by indomethacin or NS-398 treatment. However, indomethacin or NS-398 did increase urine osmolality and reduce urine volume in KO, but not control, animals. In summary, IMCD COX-2-dependent PGE2 production is increased in CD ET-1 KO mice, indicating that CD-derived ET-1 is not a primary regulator of IMCD PGE2. Furthermore, the increased PGE2 in CD ET-1 KO mice partly compensates for loss of ET-1 with respect to maintaining urinary water excretion, but not in blood pressure control.

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Nitric oxide, cyclic guanosin monophosphate, endothelin-1, erythropoietin: relationship with ambulatory blood pressure monitoring in essential hypertension

American Journal of Hypertension ◽

10.1016/s0895-7061(99)80200-3 ◽

1999 ◽

Vol 12 (4) ◽

pp. 61 ◽

Cited By ~ 1

Author(s):

M PARRINI

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Essential Hypertension ◽

Ambulatory Blood Pressure Monitoring ◽

Ambulatory Blood Pressure ◽

Blood Pressure Monitoring ◽

Pressure Monitoring ◽

Endothelin 1

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Endothelin-1, nitric oxide, serotonin and high blood pressure in male adolescents

Vascular Health and Risk Management ◽

10.2147/vhrm.s170317 ◽

2018 ◽

Vol Volume 14 ◽

pp. 213-223 ◽

Cited By ~ 4

Author(s):

Gulfiia Nagimovna Aflyatumova ◽

Razina Nigmatullina ◽

Dinara Ilgizarovna Sadykova ◽

Mariia Dmitrievna Chibireva ◽

Francesco Fugetto ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

High Blood Pressure ◽

Male Adolescents ◽

Endothelin 1

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Associations of endothelial biomarkers, nitric oxide metabolites and endothelin, with blood pressure and coronary lesions depend on cardiovascular risk and sex to mark endothelial dysfunction on the SCORE scale

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2020-0024 ◽

2020 ◽

Vol 41 (4) ◽

Author(s):

Nadezhda G. Gumanova ◽

Alexander U. Gorshkov ◽

Marina V. Klimushina ◽

Alexander Y. Kots

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Cardiovascular Risk ◽

Endothelial Dysfunction ◽

Coronary Atherosclerosis ◽

Risk Estimation ◽

High Systolic Blood Pressure ◽

Endothelin 1 ◽

Coronary Lesions ◽

Circulating Levels

AbstractObjectivesEndothelial dysfunction contributes to the onset and progression of cardiovascular diseases. However, direct associations of vasoactive mediators with cardiovascular risk are poorly understood.MethodsWe have determined associations of circulating levels of stable metabolites of nitric oxide, nitrate and nitrite (NOx), endothelin-1, and the endothelin-1/NOx ratio with blood pressure in 177 asymptomatic subjects without signs of coronary atherosclerosis; associations with blood pressure and with presence of coronary lesions were also evaluated in 457 patients suspected to have coronary heart disease with or without coronary lesions confirmed by coronary angiography. All participants were on a low nitrate diet 24 h prior to blood sampling.ResultsIn men, NOx levels were inversely correlated with blood pressure similar to women with low (0–4%) European Systematic Coronary Risk Estimation (SCORE). However, the correlation was not significant in women with high SCORE (5–8%). High systolic blood pressure over 140 mm Hg was negatively associated with NOx levels in asymptomatic men (p=0.05) but not in women. This association is disrupted in male and female patients with coronary atherosclerosis. In male patients, NOx (p=0.05), endothelin (p=0.01), and the endothelin/NOx ratio (p=0.04) were associated with presence of coronary lesions.ConclusionsThus, elevated cardiovascular risk according to SCORE over 4% in asymptomatic women, but not in men, is associated with a shift in markers of endothelial dysfunction. Presence of coronary lesions in patients is associated with significant changes in circulating levels of markers of endothelial dysfunction in men but not in women.

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Long-term nitric oxide blockade in the pregnant rat: Effects on blood pressure and plasma levels of endothelin-1

American Journal of Obstetrics and Gynecology ◽

10.1016/s0002-9378(96)70166-7 ◽

1996 ◽

Vol 175 (2) ◽

pp. 484-488 ◽

Cited By ~ 63

Author(s):

Darrell L. Edwards ◽

Chander P. Arora ◽

Dung T. Bui ◽

Lony C. Castro

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Plasma Levels ◽

Pregnant Rat ◽

Endothelin 1

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Role of the renin–angiotensin–aldosterone system in collecting duct-derived endothelin-1 regulation of blood pressureThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-028 ◽

2008 ◽

Vol 86 (6) ◽

pp. 329-336 ◽

Cited By ~ 17

Author(s):

Yuqiang Ge ◽

Yufeng Huang ◽

Donald E. Kohan

Keyword(s):

Blood Pressure ◽

Collecting Duct ◽

Plasma Renin ◽

Similar Degree ◽

Water Excretion ◽

Renin Angiotensin ◽

Endothelin 1 ◽

And Control ◽

Renin Content

Renal collecting duct (CD)-specific knockout of endothelin-1 (ET-1) causes hypertension and impaired Na excretion. A previous study noted failure to suppress the renin–angiotensin–aldosterone axis in these knockout (KO) mice, hence the current investigation was undertaken to examine the role of this system in CD ET-1 KO. Renal renin content was similar in kidneys from CD ET-1 KO and control mice during normal Na intake; high-Na intake suppressed renal renin content to a similar degree in KO and control. Plasma renin concentrations paralleled changes in renal renin content. Valsartan, an angiotensin receptor blocker (ARB), abolished the hypertension in CD ET-1 KO mice during normal Na intake. High-Na intake + ARB treatment increased blood pressure in CD ET-1 KO, but not in controls. High-Na intake was associated with reduced Na excretion in CD ET-1 KO animals, but no changes in water excretion or creatinine clearance were noted. Spironolactone, an aldosterone antagonist, also normalized blood pressure in CD ET-1 KO mice during normal Na intake, whereas high-Na intake + spironolactone raised blood pressure only in CD ET-1 KO animals. In summary, hypertension in CD ET-1 KO is partly due to angiotensin II and aldosterone. We speculate that CD-derived ET-1 may regulate, via a novel pathway, renal renin production.

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Selected Contribution: Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.5.2007 ◽

2001 ◽

Vol 90 (5) ◽

pp. 2007-2013 ◽

Cited By ~ 105

Author(s):

Ziad Tahawi ◽

Natalia Orolinova ◽

Irving G. Joshua ◽

Michael Bader ◽

Eugene C. Fletcher

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Vascular Reactivity ◽

Peripheral Resistance ◽

Separate Experiment ◽

Systemic Hypertension ◽

Endothelin 1 ◽

Arterial Blood ◽

And Control ◽

Baseline Diameter

Recurrent episodic hypoxia (EH) is a feature of sleep apnea that may be responsible for some chronic cardiovascular sequelae such as systemic hypertension. Chronic EH (8 h/day for 35 days) causes elevation of diurnal resting (unstimulated) mean arterial blood pressure (MAP) in the rat. We used in vivo video microscopy to examine arteriolar reactivity in the cremaster muscle of male Sprague-Dawley rats subjected to 35 days of EH. Cremaster muscles of EH ( n= 6) and control ( n = 6) rats were exposed to varying doses of norepinephrine (NE) (10−10 to 10−5M), ACh (10−9 to 10−5 M), and endothelin-1 (10−12 to 10−8 M). In a separate experiment, EH ( n = 5) and control ( n = 6) rats were given one dose of a nitric oxide synthase (NOS) inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 10−5 M). We also examined endothelial NOS mRNA from the kidneys of EH-stimulated and control (unstimulated) rats. Telemetry-monitored EH rats showed a 16-mmHg increase in MAP over 35 days, whereas control rats showed no change. The response to NE and endothelin-1 were similar for EH and control rats. ACh vasodilatation of arterioles in EH rats was significantly attenuated compared with that of controls. The degree of vasoconstriction in response to blockade of the nitric oxide system byl-NAME was significantly less (83% of baseline diameter with l-NAME) for arterioles of EH rats compared with that for controls (61% of baseline diameter), implying lower basal resting nitric oxide release in the EH rats. Whole kidney mRNA endothelial NOS levels were not different between groups. These data support the hypothesis that chronic elevation of blood pressure associated with EH involves increased peripheral resistance from decreased basal release or production of nitric oxide after 35 days of EH.

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