Biomedical subjects

T Tikkanen

Publications and source records attributed to T Tikkanen.

26 records · Page 2Linked to original sources

PubMed1990

Elevation of plasma atrial natriuretic peptide in rats with chronic heart failure by SCH 39370, a neutral metalloendopeptidase inhibitor.

Hormonal, renal and blood pressure effects of SCH 39370, a selective inhibitor of neutral metalloendopeptidase (endopeptidase 24.11, NEP), were studied in a chronic, congestive heart failure (CHF) model produced by coronary artery ligation in the rat. Sham-operated control rats and rats with CHF were treated either with vehicle or SCH 39370, 30 mg/kg s.c. b.i.d. for 2.5 days. Plasma levels of atrial natriuretic peptide (ANP) and urinary excretion of cyclic GMP (cGMP) were clearly raised in rats with CHF as compared with controls during vehicle treatment. SCH 39370 caused a further increase in plasma ANP in CHF rats but not in control rats. Urinary excretion of immunoreactive ANP and cGMP increased during SCH 39370 treatment both in CHF rats and in controls. SCH 39370 treatment resulted in an initial increase in urine volume in rats with CHF whereas urine sodium excretion did not change significantly. No changes in renal function due to SCH 39370 treatment were seen in control rats. Systolic blood pressure, plasma renin activity and urine excretion of catecholamine metabolites (4-hydroxy-3-methoxyphenyl acetic acid and metanephrines) did not change during SCH 39370 treatment either in controls or in CHF rats. We conclude that the NEP-inhibitory compound SCH 39370 is capable of increasing plasma ANP concentration and urinary excretion of cGMP in rats with chronic CHF. In this severe heart failure model, the possible beneficial effects of additional ANP increments may be blunted, however. NEP inhibitors offer a novel approach to study the significance of ANP elevation in chronic CHF.

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PubMed1989

Attenuated diuretic and natriuretic effects of atrial natriuretic peptide in rats with heart failure.

Plasma levels of atrial natriuretic peptide (ANP) and renal responses to ANP were examined in rats with chronic cardiac failure produced by coronary artery ligation and in sham-operated controls. Plasma ANP levels were elevated in the rats with severe cardiac failure as compared with the controls (P less than 0.001). ANP injections at the doses of 1, 5, 25 and 50 micrograms/kg increased water and sodium excretion significantly at all but the lowest dose in the controls; only the two largest doses caused clear diuresis and natriuresis in the heart failure group. The diuretic and natriuretic effects of ANP were significantly weaker at the doses of 5 and 25 micrograms/kg in the rats with heart failure as compared with the controls. We conclude, that natriuretic and diuretic effects of ANP are attenuated in this chronic heart failure mode.

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PubMed1989

Effects of captopril and NaCl loading on plasma atrial natriuretic peptide (ANP) in rat with chronic heart failure.

In order to study long term changes in plasma atrial natriuretic peptide (ANP) in chronic heart failure, plasma ANP levels were determined in rats after myocardial infarction due to coronary artery ligation and in sham-operated controls. In addition, effects of oral captopril treatment and sodium loading on plasma ANP were studied. In accordance with earlier reports plasma ANP paralleled both infarct size and signs of cardiac dysfunction. The highest plasma ANP levels were found in rats having over 45% of their left ventricle infarcted while rats with mild-to-moderate-size infarcts had only slightly elevated plasma ANP levels as compared with controls. These differences in plasma ANP levels between experimental and control groups remained remarkably stable during the three-month observation period. Plasma renin activity (PRA) was elevated in infarcted rats but no differences could be found between rats with varying infarct sizes. Captopril treatment decreased the high plasma ANP levels in rats with the largest infarcts, probably by unloading the failing heart. During increased sodium intake, plasma ANP levels increased in sham-operated controls but not in rats with heart failure. Thus, sodium loading, as compared with cardiac insufficiency, appears to be a weak stimulus for ANP release in rats. I conclude that plasma ANP is a sensitive marker, better than PRA, in long term follow-up of cardiac dysfunction.

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PubMed1987

Haemodynamic effects of atrial natriuretic peptide in rats with heart failure.

Plasma atrial natriuretic peptide (ANP), a hormone secreted by the heart, is elevated in cardiac failure. In the aim to study the role of ANP in cardiac failure, the haemodynamic response to ANP was examined in rats with chronic heart failure produced by coronary artery ligation. Plasma ANP was clearly elevated in all infarcted rats before ANP injection as compared with controls. ANP lowered the blood pressure and impaired cardiac contractility, as measured by the maximal positive value of the first derivative of the pressure signal, in a dose-dependent manner. The blood pressure lowering effects of ANP were attenuated in rats with cardiac failure. We conclude that rats with experimentally induced heart infarct are partially resistant to the haemodynamic effects of ANP.

Animals↗

PubMed1987

Elevated plasma atrial natriuretic peptide in rats with myocardial infarcts.

We measured atrial natriuretic peptide (ANP) plasma levels in rats with experimental heart failure caused by left coronary artery ligation. ANP levels were clearly higher in infarcted rats (409 +/- 59 pg/ml; mean +/- S.E.M.) than in sham-operated controls (39 +/- 6 pg/ml). Moreover, plasma ANP levels increased progressively with the severity of cardiac dysfunction and size of infarct. Increased release of ANP in post-infarction heart failure appears to be a meaningful compensatory response to control rising preload. Our results are in keeping with evidence from human studies showing increased plasma concentration of ANP in patients with congestive heart failure. This model is a useful tool to further explore the role of ANP in heart failure.

Animals↗

PubMed1987

Plasma atrial natriuretic peptide in health and disease.

The plasma concentration of atrial natriuretic peptide (ANP) in 16 healthy subjects on a free diet was 41 +/- 23 pg ml-1 (mean +/- SD) when upright and 58 +/- 27 pg ml-1 in the supine position (P less than 0.05), which confirms the concept that the supine position raises plasma ANP. Water immersion to the neck for 2 h caused a brisk diuresis, natriuresis and raised plasma ANP in 8 healthy subjects, suggesting that ANP is a mediator of diuresis and natriuresis during immersion. Dynamic exercise (50-200 W per 4 min) on a bicycle ergometer caused a gradual increase in plasma ANP in 6 healthy males, with a close correlation between the increases in plasma ANP and heart rate (r = 0.96). Thus, plasma ANP levels are increased in healthy subjects by stimuli causing an increased preload and possibly by tachycardia itself. Markedly raised plasma levels of ANP were found in patients with congestive heart failure, and upright posture caused a further rise of plasma ANP which correlated with the increase in heart rate (r = 0.87). High plasma ANP concentrations were also found in 25 patients with end-stage renal failure maintained on haemodialysis. When these patients were subdivided into those with concomitant heart failure and those with normal cardiac function, changes in plasma ANP correlated with predialysis weight gain and weight loss during dialysis, but only in patients without heart failure. In 9 infants treated by operative or pharmacological closure of persistent ductus arteriosus, high pre-treatment plasma ANP values were lowered by successful therapy, and plasma ANP correlated with the degree of left atrial distension.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1987

Plasma atrial natriuretic peptide in DOCA-NaCl-treated rats.

In order to assess the possible role of atrial natriuretic peptide (ANP) in the development of deoxycorticosterone (DOCA)-NaCl-induced hypertension, plasma immunoreactive ANP concentration was compared with sodium balance and blood pressure in NaCl- or DOCA-NaCl-treated rats. Both NaCl-and DOCA-NaCl-loading increased plasma ANP levels (to 86 +/- 8.1 and 105 +/- 12 pg ml-1 respectively; 47 +/- 6.7-60 +/- 4.6 pg ml-1 in controls), which were correlated to sodium intake and excretion. In DOCA-NaCl-treated rats, the highest ANP levels (105 +/- 12 pg ml-1) were found 4 weeks after the beginning of DOCA-NaCl treatments. Along with the development of DOCA-NaCl hypertension in 1-kidney-DOCA-NaCl-treated rats, however, plasma ANP concentration did not rise further. We conclude that secretion of ANP into the circulation is increased during DOCA-NaCl treatment. Elevated blood pressure does not stimulate ANP release in DOCA-NaCl-treated rats further.

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PubMed1980

Efficacy of captopril in experimental low renin hypertension.

Captopril (SQ 14225) had a clear antihypertensive effect in rat Heymann nephritis-DOCA-NaCl hypertension, a low renin model introduced recently, but was ineffective in 1-kidney-DOCA-NaCl hypertension although plasma renin activity (PRA) was suppressed similarly in both. Thus, the antihypertensive effect of captopril was independent of circulating renin. This result also suggests different pathogenetic mechanisms of hypertension in these two DOCA-NaCl models.

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