Atrial natriuretic peptide levels in plasma and in cardiac tissues after chronic hypoxia in rats

1989 ◽  
Vol 76 (1) ◽  
pp. 95-101 ◽  
Author(s):  
R. J. D. Winter ◽  
L. Meleagros ◽  
S. Pervez ◽  
H. Jamal ◽  
T. Krausz ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Right Ventricular ◽  
Natriuretic Peptide ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Right Ventricular Hypertrophy ◽  
Right Atrial ◽  
Adult Rats ◽  
Cardiac Tissues ◽  
Atrial Natriuretic

1. Atrial natriuretic peptide (ANP) levels were measured in cardiac tissues and in plasma from adult rats exposed to chronic alveolar hypoxia for periods of 2 h, 24 h and 7 days. Levels were also measured in rats that were maintained in hypoxia for 7 days and then returned to air for 24 h. 2. Plasma ANP was not altered at 2 h but was significantly increased at both 24 h and at 7 days. Plasma ANP in animals exposed to hypoxia for 7 days was normal 24 h after returning to air breathing, despite the persistence of indices of pulmonary hypertension. 3. No significant right atrial hypertrophy was observed under these conditions of chronic hypoxia. A reduction in right atrial ANP content was found at 24 h and was accompanied by a decrease in the number of electrondense granules per right atrial muscle cell. After exposure to hypoxia for 7 days, right atrial ANP and granule number was not different from control, and no alteration was found in right atrial ANP level after removal from the hypoxic environment. 4. No significant right ventricular hypertrophy was produced by exposure to hypoxia for 2 or 24 h. In the former group ventricular ANP had decreased significantly compared with control. Right ventricular hypertrophy was found in both the hypoxic groups after exposure for 7 days, when selective increases in right ventricular ANP content were found. 5. These findings are consistent with the hypothesis that ANP release occurs on exposure to chronic hypoxia and is independent of the associated cardiac hypertrophy and pulmonary vascular remodelling. The findings may have relevance to the natriuresis and reported changes in the renin-angiotensin-aldosterone axis under hypoxic conditions.

Abstract 15303: Dimethylarginine Dimethylaminohydrolase-1 is Not Involved in Chronic Hypoxic Pulmonary Hypertension and Right Ventricular Hypertrophy in Mice

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Juliane Hannemann ◽  
Antonia Glatzel ◽  
Jonas Hillig ◽  
Julia Zummack ◽  
Rainer H Boeger
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Right Ventricular Hypertrophy ◽  
Cardiomyocyte Hypertrophy ◽  
No Production ◽  
Knock Out ◽  
Knock Out Mice ◽  
Adma Concentration

Introduction: Chronic hypoxia causes persistent pulmonary vasoconstriction and leads to pulmonary hypertension and right ventricular hypertrophy. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis; its level increases in hypoxia concomitantly with reduced activity of dimethylarginine dimethylaminohydrolases (DDAH-1 and DDAH-2), the enzymes metabolizing ADMA. DDAH knockout models may therefore help to understand the pathophysiological roles of this enzyme and its substrate, ADMA, in the development of hypoxia-associated pulmonary hypertension. Hypothesis: We hypothesized that DDAH1 knock-out mice have an attenuated hypoxia-induced elevation of ADMA and reduced right ventricular hypertrophy. Methods: DDAH1 knock-out mice (KO) and their wild-type littermates (WT) were subjected to normoxia (NX) or hypoxia (HX) during 21 days. We measured ADMA concentration in plasma, DDAH1 and DDAH2 expression in the lung, right ventricular hypertrophy by the Fulton index, cardiomyocyte hypertrophy by dystrophin staining of heart tissues, and muscularization of pulmonary arterioles by CD31 and α-actin staining of lung sections. Results: DDAH1 KO mice had higher ADMA concentration than WT under NX (2.31±0.33 μmol/l vs. 1.20±0.17 μmol/l; p < 0.05). ADMA significantly increased in WT-HX (to 1.74±0.86 μmol/l; p < 0.05 vs. normoxia), whilst it did not further increase in KO-HX (2.58±0.58 μmol/l; p = n.s.). This was paralleled by a 38±13% reduction in DDAH1 mRNA but not DDAH2 mRNA expression, and reduced DDAH protein expression. We observed right ventricular hypertrophy under hypoxia in both, WT and KO mice, with no significant differences between both genotypes. Further, cardiomyocyte hypertrophy and pulmonary arteriolar muscularization were significantly increased by hypoxia, but not significantly different between WT and KO mice. Conclusions: We conclude that chronic hypoxia causes an elevation of ADMA, which impairs NO production and leads to endothelial dysfunction and vasoconstriction. Downregulation of DDAH expression and activity may be involved in this; however, knockout of DDAH1 does not modify the pathophysiological changes in remodeling of the pulmonary vasculature and the right ventricle.

scholarly journals Exogenous Ghrelin Attenuates the Progression of Chronic Hypoxia-Induced Pulmonary Hypertension in Conscious Rats

Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 237-244 ◽  
Author(s):  
Daryl O. Schwenke ◽  
Takeshi Tokudome ◽  
Mikiyasu Shirai ◽  
Hiroshi Hosoda ◽  
Takeshi Horio ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Endothelial Nitric Oxide Synthase ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Arterial ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Chronic exposure to hypoxia, a common adverse consequence of most pulmonary disorders, can lead to a sustained increase in pulmonary arterial pressure (PAP), right ventricular hypertrophy, and is, therefore, closely associated with heart failure and increased mortality. Ghrelin, originally identified as an endogenous GH secretagogue, has recently been shown to possess potent vasodilator properties, likely involving modulation of the vascular endothelium and its associated vasoactive peptides. In this study we hypothesized that ghrelin would impede the pathogenesis of pulmonary arterial hypertension during chronic hypoxia (CH). PAP was continuously measured using radiotelemetry, in conscious male Sprague Dawley rats, in normoxia and during 2-wk CH (10% O2). During this hypoxic period, rats received a daily sc injection of either saline or ghrelin (150 μg/kg). Subsequently, heart and lung samples were collected for morphological, histological, and molecular analyses. CH significantly elevated PAP in saline-treated rats, increased wall thickness of peripheral pulmonary arteries, and, consequently, induced right ventricular hypertrophy. In these rats, CH also led to the overexpression of endothelial nitric oxide synthase mRNA and protein, as well as endothelin-1 mRNA within the lung. Exogenous ghrelin administration attenuated the CH-induced overexpression of endothelial nitric oxide synthase mRNA and protein, as well as endothelin-1 mRNA. Consequently, ghrelin significantly attenuated the development of pulmonary arterial hypertension, pulmonary vascular remodeling, and right ventricular hypertrophy. These results demonstrate the therapeutic benefits of ghrelin for impeding the pathogenesis of pulmonary hypertension and right ventricular hypertrophy, particularly in subjects prone to CH (e.g. pulmonary disorders).

Hemodynamic and renal effects of low-dose infusions of atrial peptide in awake dogs

1988 ◽  
Vol 254 (2) ◽  
pp. R161-R169 ◽  
Author(s):  
P. Bie ◽  
B. C. Wang ◽  
R. J. Leadley ◽  
K. L. Goetz
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Plasma Renin ◽  
Urine Flow ◽  
Right Atrial ◽  
Experimental Protocols ◽  
Cardiac Filling ◽  
Left And Right ◽  
Atrial Natriuretic

The effects of alpha-human atrial natriuretic peptide (alpha-hANP) on cardiovascular and renal function in conscious dogs were evaluated in two experimental protocols. In one protocol, alpha-hANP was infused intravenously at increasing rates of 50, 100, and 200 ng.min-1.kg-1 (stepup infusion) during successive 20-min periods. The greatest responses occurred during the final 20-min period of the stepup infusion when the plasma concentration of immunoreactive atrial natriuretic peptide (irANP) was increased by 44-fold over preinfusion values; pressures in the aorta and both atria were decreased at this time, whereas glomerular filtration rate, urine flow, and sodium excretion were increased. In a second protocol, alpha-hANP was infused for 1 h at constant rates of either 12.5, 25, or 50 ng.min-1.kg-1; these constant infusions increased plasma irANP by 3-, 7-, and 12-fold, respectively. Each infusion rate decreased left and right atrial pressures and increased urine flow and sodium excretion. The two lowest infusion rates elevated plasma irANP to levels that would be expected to occur only during unusual physiological, or perhaps pathophysiological, conditions. The two highest infusion rates decreased plasma renin activity. Nevertheless, the accompanying maximal increases in sodium excretion were modest (41-72%). These data imply that small changes in circulating atrial peptides that presumably occur under normal physiological conditions would not have a dominant effect on the regulation of sodium excretion; the peptides may, however, play a modulatory role on sodium excretion under these conditions. It remains to be determined whether the ability of atrial peptides to lower cardiac filling pressures is of physiological significance.

Mechanism for decrease in cardiac output with atrial natriuretic peptide in dogs

1989 ◽  
Vol 256 (3) ◽  
pp. H760-H765 ◽  
Author(s):  
R. W. Lee ◽  
S. Goldman
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Blood Volume ◽  
Left Ventricular ◽  
Right Atrial ◽  
Total Blood Volume ◽  
Total Blood ◽  
Atrial Natriuretic

To examine the mechanism by which atrial natriuretic peptide (ANP) decreases cardiac output, we studied changes in the heart, peripheral circulation, and blood flow distribution in eight dogs. ANP was given as a bolus (3.0 micrograms/kg) followed by an infusion of 0.3 microgram.kg-1.min-1. ANP did not change heart rate, total peripheral vascular resistance, and the first derivative of left ventricular pressure but decreased mean aortic pressure from 91 +/- 4 to 76 +/- 3 mmHg (P less than 0.001) and cardiac output from 153 +/- 15 to 130 +/- 9 ml.kg-1.min-1 (P less than 0.02). Right atrial pressure and left ventricular end-diastolic pressure also decreased. Mean circulatory filling pressure decreased from 7.1 +/- 0.3 to 6.0 +/- 0.3 mmHg (P less than 0.001), but venous compliance and unstressed vascular volume did not change. Resistance to venous return increased from 0.056 +/- 0.008 to 0.063 +/- 0.010 mmHg.ml-1.kg.min (P less than 0.05). Arterial compliance increased from 0.060 +/- 0.003 to 0.072 +/- 0.004 ml.mmHg-1.kg-1 (P less than 0.02). Total blood volume and central blood volume decreased from 82.2 +/- 3.1 to 76.2 +/- 4.6 and from 19.8 +/- 0.8 to 17.6 +/- 0.6 ml/kg (P less than 0.02), respectively. Blood flow increased to the kidneys. We conclude that ANP decreases cardiac output by decreasing total blood volume. This results in a lower operating pressure and volume in the venous capacitance system with no significant venodilating effects. Cardiac factors and a redistribution of flow to the splanchnic organs are not important mechanisms to explain the decrease in cardiac output with ANP.

scholarly journals Renal Effects of Atrial Natriuretic Peptide Infusion in Young and Adult Rats

1988 ◽  
Vol 24 (3) ◽  
pp. 333-337 ◽  
Author(s):  
Robert L Chevalier ◽  
R Ariel Gomez ◽  
Robert M Carey ◽  
Michael J Peach ◽  
Joel M Linden ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Adult Rats ◽  
Renal Effects ◽  
Atrial Natriuretic
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