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Biomedical subjects

M Haass

Publications and source records attributed to M Haass.

At least 73 records · Page 4Linked to original sources
PubMed1990

Plasma concentrations of atrial natriuretic peptide during physical exercise in patients with congestive heart failure.

Plasma concentrations of atrial natriuretic peptide (ANP) were measured in 25 patients with organic heart disease during physical exercise (baseline and maximum workload) in order to investigate if the responsiveness of stimulated release of ANP is still preserved in patients with heart failure and chronically elevated cardiac filling pressures. Since plasma concentrations of ANP are known to be positively correlated with mean right atrial pressures (RAP), the patients were divided into two groups according to their resting RAP; group I; those with normal RAP (less than or equal to 5 mmHg; n = 11); group II; those with elevated RAP (greater than 5 mmHg; n = 14). Under baseline conditions RAP (3.2 +/- 0.4 mmHg vs. 8.8 +/- 0.7 mmHg; p less than 0.01), pulmonary artery diastolic pressure (PADP; 9.5 +/- 0.9 mmHg vs. 17.9 +/- 1.8 pg/ml; p less than 0.01), and plasma ANP levels (128 +/- 19 pg/ml vs. 204 +/- 60 pg/ml; p less than 0.06) were significantly lower in group I than in group II. Both at rest and during maximum workload, plasma ANP concentrations were closely related to RAP, PADP, and mean pulmonary artery pressures in both groups. During exercise in all patients, RAP and PADP significantly increased, as well as plasma ANP concentrations. Similar increments in plasma ANP concentrations were accompanied by greater changes in RAP in group II than in group I. However, identical changes in PADP lead to identical increments in plasma ANP concentrations in both groups. In conclusion, the increments of plasma ANP concentrations during physical exercise were independent of the resting values of PADP, RAP, and plasma ANP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Atrial natriuretic peptide mRNA in patients with heart disease.

The regulation of atrial natriuretic peptide (ANP) synthesis within cardiac atrial myocytes was investigated in 8 patients undergoing cardiac surgery (valve replacement or coronary bypass graft). Hemodynamic data were obtained during cardiac catheterization and venous plasma samples for ANP were withdrawn prior to surgery. Probes for determination of tissue ANP levels and ANPmRNA concentrations were taken from the right atrium. Both plasma ANP (r = 0.75; P less than .05) and ANPmRNA (r = 0.86; P less than .01) were closely related to mean pulmonary artery pressure. ANPmRNA was also related to plasma ANP (r = 0.60; P less than .07). However, no significant relationships were obtained between either plasma ANP or ANPmRNA and right atrial ANP concentrations. These data suggest that right atrial ANP synthesis is regulated by cardiac filling pressures and possibly by plasma ANP levels, independent from corresponding ANP tissue concentrations.

Aged↗
PubMed1990

Role of calcium channels and protein kinase C for release of norepinephrine and neuropeptide Y.

The role of calcium for the release of norepinephrine (NE, determined by high-pressure liquid chromatography) and neuropeptide Y (NPY, determined by radioimmunoassay) was investigated in guinea pig perfused hearts with intact sympathetic innervation. In the presence of extracellular calcium (1.85 mM), electrical stimulation of the left stellate ganglion (12 Hz, 1 min) induced a closely related release of NE and NPY with the molar ratio of approximately 400-600 (NE) to 1 (NPY). The stimulation-evoked overflow of both transmitters was dependent from the extracellular calcium concentration and was almost completely suppressed by calcium-free perfusion. The corelease of both transmitters was not affected by the L-type calcium channel blocker felodipine (1-10 microM). However, the overflow of NE and NPY was markedly attenuated by the unselective calcium antagonist flunarizine (1-10 microM) and completely prevented by the neuronal (N-type) calcium channel blockers omega-conotoxin (1-100 nM) and cadmium chloride (10-100 microM), indicating a key role for N-type calcium channels in the exocytotic release of transmitters from cardiac sympathetic nerve fibers. Possibly due to unspecific actions, such as interference with sodium channels or uptake1-blocking properties, the phenylalkylamines verapamil (0.01-10 microM) and gallopamil (1-10 microM) reduced NPY overflow with only a minor effect on NE overflow. The stimulation-induced transmitter release was increased up to twofold by activation of protein kinase C (phorbol 12-myristate 13-acetate, 3 nM-3 microM) and completely suppressed by inhibition of protein kinase C (polymyxin B, 100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Neuropeptide Y differentiates between exocytotic and nonexocytotic noradrenaline release in guinea-pig heart.

The overflow of neuropeptide Y (NPY; radioimmunoassay), noradrenaline and dihydroxyphenylethylenglycol (DOPEG; high pressure liquid chromatography) from guinea-pig perfused hearts was investigated in relationship to exocytotic and nonexocytotic release mechanisms. Exocytotic release: Electrical stimulation of the left stellate ganglion (12 Hz; 1 min) evoked a calcium-dependent overflow of noradrenaline and NPY, that was accompanied by a minor and prolonged increase in DOPEG overflow. This increase in DOPEG overflow was attenuated by blockade of neuronal amine re-uptake. In the presence of calcium, a closely related co-release of noradrenaline and NPY was also observed during administration of veratridine (10 microM); it was completely prevented by tetrodotoxin (1 microM). Nonexocytotic release: In the absence of extracellular calcium, veratridine (30 microM) induced noradrenaline overflow only when combined with the reserpine-like agent Ro 4-1284 (10 microM). This overflow was accompanied by efflux of DOPEG, but not of NPY. Similarily, tyramine (1-100 microM) induced a calcium-independent concomitant overflow of both noradrenaline and DOPEG, but not of NPY. During anoxic and glucose-free perfusion a predominantly calcium-independent overflow of noradrenaline was observed; only in the presence of extracellular calcium was this overflow accompanied by a minor overflow of NPY. Noradrenaline overflow, induced by veratridine plus Ro 4-1284 (in the absence of calcium), by tyramine, or by anoxia, was suppressed by blockade of neuronal amine re-uptake, and was, therefore, mediated by reversed transmembrane amine transport by the neuronal uptake carrier. The results indicate that NPY is co-released with noradrenaline only during calcium-dependent exocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1989

Long-term imipramine treatment potentiates m-chlorophenylpiperazine-induced changes in prolactin but not corticosterone or growth hormone levels in rats.

Intravenous administration of m-chlorophenylpiperazine (m-CPP, a selective 5-HT agonist) to rats produced increases in plasma prolactin and corticosterone and a decrease in plasma growth hormone concentrations. Long-term but not short-term imipramine treatment potentiated m-CPP's effect on plasma prolactin, but not its effects on corticosterone or growth hormone. Short-term or long-term imipramine treatment did not produce significant changes in baseline levels of prolactin, corticosterone or growth hormone. These findings are compatible with development of functional supersensitivity of 5-HT receptors mediating prolactin release. Lack of potentiation of m-CPP's effects on corticosterone and growth hormone following long-term imipramine treatment suggests either differential regulation of these hormones by serotonergic and possibly other mechanisms, or different 5-HT receptor subtypes mediating the release of these hormones. Alternatively, adaptive changes in other aminergic neurotransmitter mechanisms such as the noradrenergic system may account for the differential effect of long-term imipramine treatment on m-CPP-induced neuroendocrine changes.

Animals↗
PubMed1989

Atrial natriuretic factor. Its possible role in hypertension and congestive heart failure.

The atrial natriuretic factor (ANF) is a circulating peptide, consisting of 24 to 28 amino acids. Atrial natriuretic factor is synthetized in atrial cardiomyocytes and stored in specific cytoplasmatic granules. It possesses potent diuretic, natriuretic, and vasorelexant properties. The possible role of ANF in the pathogenesis of hypertension and heart failure was investigated in animal models and in men. We were able to show that the release of ANF from cardiac atria is positively correlated with atrial pressures in both men and rats. In experimental studies, plasma levels of ANF measured by radioimmunoassay, were increased by up to four-fold after acute blood volume expansion. Atrial natriuretic factor release in response to volume loading was markedly attenuated in four-week-old spontaneously hypertensive rats as compared to age-matched normotensive Wistar-Kyoto rats, but a similar responsiveness was found in 16-week-old rats of both strains. This finding can be reconciled with the hypothesis that ANF plays a pathophysiological role in initiating but not maintaining high blood pressure. Clinical studies demonstrate elevated plasma concentrations of ANF in patients with organic heart disease. Further increments in plasma levels of ANF were obtained during physical exercise and after acute volume loading. In patients with congestive cardiomyopathy, the elevated plasma concentrations of ANF reached almost normal levels following improvement of their hemodynamic disturbances after treatment with converting-enzyme inhibitors. These findings suggest that in patients with organic heart disease, plasma concentrations of ANF reflect the hemodynamic burden of the heart and may, therefore, be used as a noninvasive marker of the efficacy of the current cardiac therapy.

Animals↗
PubMed1988

Role of right and left atrial dimensions for release of atrial natriuretic peptide in left-sided valvular heart disease and idiopathic dilated cardiomyopathy.

To evaluate the role of atrial dimensions for release of atrial natriuretic peptide (ANP), right and left atrial dimensions (cross-sections) were determined by 2-dimensional echocardiography in 50 patients with left-sided valvular heart disease or idiopathic dilated cardiomyopathy. All patients underwent right- and left-sided heart catheterization with measurement of central hemodynamics. Plasma samples for ANP were withdrawn from femoral vein (ANPv) and ascending aorta. An estimate of right and left meridional atrial wall stress was derived by multiplying cross-sectional areas with pressures of the respective atria. As expected ANPv was closely related to mean right (r = 0.63; p less than 0.001; n = 50) and left atrial pressures (r = 0.61; p less than 0.001; n = 47). Furthermore, a positive correlation between ANPv and right (r = 0.56; p less than 0.001; n = 48) and left (r = 0.30; p less than 0.05; n = 48) atrial cross-sections was obtained. Finally, an excellent relation was found between ANPv and right (r = 0.73; p less than 0.001; n = 48) as well as left (r = 0.58; p less than 0.001; n = 44) meridional atrial wall stress, indicating that atrial wall stress rather than atrial pressures or dimensions alone determines plasma ANP concentrations. However, for identical right and left meridional atrial wall stress 3- to 4-times higher plasma ANPv levels were obtained in patients with idiopathic dilated cardiomyopathy than in patients with left-sided valvular heart disease. This indicates that release of ANP to the same stimulus may be modulated by the nature of the underlying heart disease.

Adult↗
PubMed1988

Humoral adaptation mechanisms and clinical outcome during vasodilator therapy.

Administration of hydralazine and isosorbide dinitrate leads to a reduction of one-year mortality by 38%. However, a major disappointment has been the inability to predict the individual patient's response to these drugs. The aim of the present study, therefore, was to evaluate possible predictors for a favourable response to hydralazine treatment on the basis of the acute humoral and haemodynamic response to the drug. Stroke volume increased in all 37 patients with severe left ventricular dysfunction in response to acute intravenous hydralazine (0.4 mg kg-1). However, when re-investigated after 2 months of chronic oral hydralazine therapy, sustained haemodynamic and clinical improvement was observed in only 16 patients. Pretreatment values of either left ventricular filling pressure, cardiac index or systemic vascular resistance were not useful in predicting the outcome of treatment. However, when patients were subdivided on the basis of their heart rate response to acute hydralazine, better discrimination for a beneficial response, was possible. It is concluded that the haemodynamic and humoral responses to acute intravenous hydralazine allow discrimination between patients not responding to chronic vasodilator treatment and those who are likely to benefit. A reflex excitation of sympathetic outflow in response to acute vasodilation (indicated by a reflex acceleration of heart rate and increase in plasma noradrenaline levels) characterised best those patients who did not benefit from oral hydralazine. The data indicate a detrimental role of reflex sympathetic stimulation which may blunt at least part of the direct beneficial drug-induced effect in chronic vasodilator therapy.

Atrial Natriuretic Factor↗
PubMed1988

[Does the measurement of plasma ANP have a diagnostic or prognostic value in patients with organic heart disease?].

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with organic heart disease undergoing diagnostic cardiac catheterization. Independent of nature and duration of the disease (valvular heart disease, congestive cardiomyopathy) plasma ANP levels were closely related to the severity of cardiac failure. Furthermore, plasma ANP levels were found to be negatively correlated with the cardiac index and to be positively correlated with right and/or left atrial and with pulmonary artery pressures. During physical exercise (bicycle ergometer) a marked increase of plasma ANP levels was observed, which was closely related to increments in mean pulmonary artery pressure. This rise in plasma ANP levels during physical exercise was not attenuated in patients with already elevated resting plasma concentrations of ANP. In patients with congestive cardiomyopathy, afterload-reduction by ACE-inhibition resulted in changes of central hemodynamics, which were closely reflected by venous concentrations of ANP. The measurement of plasma ANP levels may serve as an indicator of the severity of cardiac failure. Plasma concentrations of ANP, however, are neither helpful in establishing the etiology of the underlying heart disease nor in differentiating left and right heart failure. However, in cases of already established organic heart disease plasma ANP levels may be used as a marker for assessing the efficacy of the therapeutic regimen.

Atrial Natriuretic Factor↗
PubMed1988

Nicotine-induced release of noradrenaline and neuropeptide Y in guinea pig heart.

The effect of nicotine on the release of noradrenaline and neuropeptide Y was investigated in isolated perfused guinea pig hearts (Langendorff technique). Endogenous noradrenaline, dihydroxyphenylglycol (both determined by high pressure liquid chromatography) and neuropeptide Y (determined by radioimmunoassay) were measured in the coronary venous effluent following the addition of nicotine to the perfusate. Nicotine (2 microM to 2 mM) dose-dependently increased both noradrenaline and neuropeptide Y overflow, and the release of both transmitters was closely correlated (r = 0.81). Despite ongoing nicotine administration noradrenaline and neuropeptide Y levels returned to basal values within 6 min of continuous nicotine administration indicating rapid tachyphylaxis to the effect of nicotine. The nicotine-induced release of noradrenaline and neuropeptide Y required the presence of extracellular calcium, and the release of both substances was suppressed by hexamethonium or by low concentrations of the inhibitors of the neuronal noradrenaline uptake (uptake1) desipramine and nisoxetine. Nicotine did not result in a significant release of the noradrenaline metabolite dihydroxyphenylglycol which was utilized as an indicator of free axoplasmic amine levels. The close correlation between noradrenaline and neuropeptide Y release, its calcium dependence, and the lack of dihydroxyphenylglycol overflow are in agreement with the concept of a common and exocytotic release of noradrenaline and neuropeptide Y induced by nicotine.

Animals↗
PubMed1987

Anterior pituitary gland modulates the release of atrial natriuretic peptides from cardiac atria.

Myocytes in the atria contain a prohormone that gives rise to atrial natriuretic peptides (ANP), which have intrinsic hemodynamic regulatory activity. Little is known about mechanisms regulating ANP release. In rats with indwelling catheters, acute blood volume expansion with 5% (wt/vol) dextrose increases the amount of circulating immunoreactive ANP by a factor of 2-3, as determined by radioimmunoassay. Pithing, which both removes neurogenic influences and interrupts humoral influences of the brain and pituitary gland on the heart, completely blocked stimulus-induced release of ANP. Because our studies using pharmacological blockade of the autonomic nervous system had suggested that neurogenic mechanisms do not play a major role in ANP release, we sought a humoral mechanism involved in ANP secretion. Basal and stimulated release of ANP were significantly blunted in hypophysectomized rats (8 days after operation) but were completely restored when the resected anterior pituitary was reimplanted under the kidney capsule. This suggests that hormones of anterior pituitary origin are required for ANP secretion in response to acute volume loading.

Adrenalectomy↗
PubMed1987

Role of autonomic nervous system and vasoactive hormones in the release of atrial natriuretic peptides in conscious rats.

Atrial natriuretic peptides (ANPs) have been implicated in volume homeostasis and blood pressure regulation; however, little is known about factors regulating the release of ANPs. We therefore examined the roles of the sympathetic and parasympathetic nervous systems, the renin-angiotensin system, and vasopressin in the release of ANPs, under basal conditions and after acute blood volume expansion or acute salt loading in conscious rats. Plasma concentrations of immunoreactive ANPs (ir-ANPs) were measured by specific radioimmunoassay. Both acute blood volume expansion and acute salt loading increased basal plasma levels of ir-ANPs (90.4 +/- 5.2 pg/ml) four- to fivefold within 2 min. Basal and stimulated plasma levels of ir-ANPs were unaltered by pretreatment with methylatropine or with propranolol or by ganglionic blockade with hexamethonium. Total adrenergic blockade (combined treatment with yohimbine, prazosin, and propranolol) had no effect on basal or salt loading-stimulated plasma levels of ir-ANPs and slightly attenuated blood volume expansion-induced release of ANPs. Ganglionic blockade with chlorisondamine tripled basal plasma concentrations of ir-ANPs but had no effect on stimulation-induced release of ANPs. Acute blockade of the renin-angiotensin system with captopril or infusion of saralasin or pretreatment with a vasopressin pressor antagonist had no effect on basal or stimulated release of ANPs. Following intravenous bolus injections of graded doses of l-norepinephrine, angiotensin II, and vasopressin, mean arterial pressure and plasma levels of ir-ANPs increased in a dose-dependent manner. In conclusion, plasma concentrations of ir-ANPs can be acutely elevated by several physiological stimuli: volume expansion; salt loading; and pressor hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Neuropeptide Y is a potent vasoconstrictor and a cardiodepressant in rat.

Neuropeptide Y (NPY) is contained in and coreleased with norepinephrine (NE) from sympathetic nerves innervating vascular and cardiac tissues. The effects of NPY infusion on systemic hemodynamics and cardiac performance were compared with those of NE in conscious and pentobarbital sodium-anesthetized rats. A 10-min infusion of NPY (2 nmol.kg-1.min-1) decreased cardiac index (CI) 20% and stroke volume index (SVI) 9% with increases of 20% in mean arterial pressure (MAP) and 48% in total peripheral resistance (TPR). Conversely, NE (1.0 microgram.kg-1.min-1) increased SVI 14%, MAP 29%, and TRP 26%, with no change in CI. Heart rates decreased similarly (approximately 60 beats/min) but only NE-induced bradycardia was reversible by methylatropine nitrate. In anesthetized rats NPY (0.1 nmol.kg-1.min-1) increased left ventricular end-diastolic pressure (LVEDP) 20 +/- 10 mmHg (means +/- SD, n = 7) and decreased dP/dt by 8 +/- 6%. NE (0.07 microgram.kg-1.min-1) produced an equivalent pressor response, however, dP/dt rose 22 +/- 10% whereas LVEDP increased significantly less than with NPY. Thus NPY is a potent vasoconstrictor exerting similar effects to NE on MAP and TPR but, unlike NE, possesses negative inotropic and chronotropic activity.

Animals↗
PubMed1986

Circulating atrial natriuretic peptides in conscious rats: regulation of release by multiple factors.

Cardiocytes in the atria contain a prohormone that gives rise to atrial natriuretic peptides (ANP's), which have intrinsic hemodynamic regulatory activity. The distribution of ANP's in the brain suggests the involvement of these peptides in central cardiovascular regulation. In conscious rats with chronic indwelling catheters, volume loading with isotonic saline or glucose increased the amount of circulating immunoreactive ANP's by a factor of 4 to 5, as determined by radioimmunoassay. Hyperosmotic challenge with a hypertonic NaCl solution or anesthesia with halothane caused similar increases in plasma ANP's. Results obtained with the denervated-heart preparation indicate that neuronal influences are important in the release of ANP's induced by volume loading. As judged from reversed-phase high-performance liquid chromatography of extracted plasma and radioimmunoassay of collected fractions, the circulating physiologically important ANP's in the conscious rodent appear to be alpha-rANP(5-28) (atriopeptin III) and either alpha-rANP(3-28) [ANF(8-33)] or alpha-rANP(1-28) (ANF).

Anesthesia↗
PubMed1986

Neuropeptide Y and peptide YY mediate nonadrenergic vasoconstriction and modulate sympathetic responses in rats.

The modulation of cardiovascular sympathetic responses by neuropeptide Y (NPY) and peptide YY (PYY) was assessed in vivo, in pithed rats. Both peptides (0.02-2 nmol/kg) caused similar dose-dependent pressor responses, resistant to adrenergic blockade but antagonized by the calcium channel blocker, nifedipine. Only NPY, at the lowest dose, slightly accelerated heart rate (by 10 +/- 4 beats/min). At the pressor dose (0.6 nmol/kg) but not subpressor dose (0.2 nmol/kg), the increase in blood pressure induced by stimulation of the sympathetic outflow (ST: 0.3 Hz, 50 V, 1 min) was attenuated by PYY (by 40%), whereas ST-evoked tachycardia was reduced by NPY (by 35%). Neither NPY- nor PYY-pretreatment affected ST-induced increments in plasma norepinephrine (NE) and epinephrine concentrations. In addition, regional hemodynamic effects of NPY were studied in conscious rats instrumented with Doppler flow probes. The hypertension caused by NPY was attended by reflex bradycardia and marked rise in peripheral vascular resistance in renal (+ 233 +/- 59%), superior mesenteric (+ 183 +/- 65%) and hindquarter (+ 65 +/- 10%) circulation. The pattern of hemodynamic responses of NPY was similar to that of NE but, unlike the latter, persisted after adrenergic blockade.

Animals↗
PubMed1986

Plasma levels of atrial natriuretic peptides in conscious adult spontaneously hypertensive rats.

The effects of acute volume expansion and acute salt loading on the plasma levels of immunoreactive atrial natriuretic peptides (ir-ANP's) were investigated in conscious adult (16 weeks) Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Basal plasma concentrations of ir-ANP's were similar (108 +/- 9 pg/ml and 105 +/- 8 pg/ml, respectively) in hypertensive and normotensive rats. In both strains mean arterial pressure, heart rate and plasma catecholamines were unaltered by acute volume expansion but significantly elevated by acute salt loading. However, both acute volume expansion and acute salt loading increased plasma concentrations of ir-ANP's similarily in SHR and WKY rats, independent of blood pressure or plasma catecholamine levels. Our findings show that chronic hypertension in SHR does not result in changes in basal or VOL- and SAL-stimulated levels of circulating ir-ANP's.

Animals↗
PubMed1986

Interactions of atrial natriuretic peptide with the sympathetic and endocrine systems in the pithed rat.

We have found previously that atrial natriuretic peptides (ANPs) attenuate pressor response to alpha-2 adrenoceptor agonists but not to alpha-1 agonists in the pithed rat. We have now investigated the effects of ANP on other pressor agonists and on sympathetically mediated responses in rats. Bolus-injected ANP (0.1-10.0 nmol/kg) attenuated pressor responses to angiotensin II, vasopressin and alpha-2 adrenoceptor-mediated component of norepinephrine (NE)-induced responses (up to 17, 27 and 15%, respectively) in pithed rats. The threshold antipressor dose of ANP was the lowest for angiotensin II (comparable to normal levels of circulating ANP-immunoreactivity in rats) whereas it was higher for vasopressin and NE (comparable to plasma ANP-immunoreactivity stimulated by volume expansion). A 30-min infusion of ANP (0.15 nmol/kg/min) shifted the NE dose-pressor response curve 1.7-fold to the right. Conversely, neither that rate of ANP infusion nor the highest dose of bolus injected ANP altered pressor and plasma NE responses to sympathetic stimulation in demedullated pithed rats. However, at higher infusion rates, ANP reduced sympathetic stimulation-induced pressor responses (2.6-fold) and elevations of plasma NE levels (1.6-fold), without altering NE clearance. Similarly in conscious rats, ANP infusion prevented a reflex increase in plasma NE concentrations associated with hypotension. Thus, although the intrajunctional alpha-1 and presynaptic alpha-2 adrenoceptors are inaccessible to the short term bolus-induced elevation of circulating ANP during longer term increases in plasma ANP, it does reach the junction, reduces NE release and limits effects of receptor activation, possibly by diminishing Ca++ entry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗