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

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

The FASEB Journal ◽

10.1096/fasebj.21.6.a894-b ◽

2007 ◽

Vol 21 (6) ◽

Author(s):

Donald E. Kohan ◽

Yuqiang Ge ◽

Markus P. Schneider ◽

David M. Pollock ◽

Jennifer S. Pollock

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Collecting Duct ◽

Endothelin 1

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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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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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