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Biomedical subjects

J Genest

Publications and source records attributed to J Genest.

At least 109 records · Page 6Linked to original sources
PubMed1988

Effects and pharmacokinetics of bolus injections of atrial natriuretic factor in normal volunteers.

The aim of this study was to examine the hemodynamic, renal, and endocrine effects of exogenous human atrial natriuretic factor (ANF), together with its pharmacokinetics, in healthy volunteers. Ten subjects participated in this study, in which the effects of a single bolus dose of ANF and of a matched vehicle injection were compared under a 135 mmol/day sodium intake. Doses of 3, 12.5, and 25 micrograms of ANF were given to 1 subject each, and doses of 50 and 100 micrograms were given to 4 and 3 subjects, respectively. Significantly, hemodynamic changes occurred at the 100 micrograms dose, when mean blood pressure decreased by 15% and heart rate increased reciprocally. Diuresis and natriuresis tended to increase following 50 micrograms but increased significantly and in a prolonged fashion following 100 micrograms of ANF. Atrial natriuretic factor did not cause significant changes in plasma catecholamine, renin activity, and aldosterone levels at any dose, although aldosterone tended to decrease. Plasma arginine-vasopressin concentrations decreased significantly following 100 micrograms. Plasma cyclic GMP levels increased in all subjects and in a dose-dependent fashion. Plasma ANF concentrations peaked 3-5 min following the bolus injection and returned toward baseline values within 10-60 min. Although with doses of less than or equal to 50 micrograms plasma ANF levels increased up to 8 to 50-fold, compared to baseline values, the only significant change was the increase in plasma cyclic GMP levels, perhaps because the effects of ANF were successfully masked by counter-regulatory mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Vasorelaxation and vascular binding sites for atrial natriuretic peptide in pregnant rats.

To investigate the role of atrial natriuretic peptide (ANP) in pregnancy, we measured, in cyclic and pregnant female rats (9- and 21-days pregnant), the vascular responsiveness to ANP using helical strips of the thoracic aorta, the binding characteristics of 125I-labeled ANP in a membrane preparation of the mesenteric vascular bed, and the plasma level and the atrial content of immunoreactive ANP (IR-ANP). On aorta strips, concentration-response (C-R) curves to phenylephrine (PE) were measured and were slightly displaced to the right in the aorta of both groups of pregnant rats in comparison with the cyclic rats. There was a potentiation of the relaxant response of ANP on the PE-precontracted aortic strips of 9-day pregnant rats but it was not statistically modified in tissues of 21-day pregnant rats in comparison with strips from cyclic rats. The number of binding sites (Bmax) for ANP in the mesenteric vascular bed was similar in cyclic rats and the two groups of pregnant rats. The dissociation constant (KD) of ANP was lower in 9-day pregnant rats than in cyclic and 21-day pregnant ones. Plasma IR-ANP was not different in 9-day pregnant rats and cyclic rats but was markedly decreased at the end of gestation. Atrial content of IR-ANP increased at the end of gestation, but not in midpregnancy in comparison with cyclic rats. These results indicate that despite the reported important increase in blood volume during gestation the secretion of ANP is not increased and suggest that the ANP-volume relationship is reset during pregnancy in the rat.

Animals↗
PubMed1988

The atrial natriuretic factor in hypertension. State of the art lecture.

Studies were conducted to assess the effects of bolus injections and infusions of human atrial natriuretic factor (ANF) in control subjects and patients with mild essential hypertension, and to measure plasma immunoreactive ANF (irANF) concentration in a large group of patients with essential hypertension. The results are compared with those obtained by other groups on the measurements of plasma irANF in hypertensive patients. It appears that plasma irANF concentrations are not increased in patients with mild essential hypertension despite the evidence of increased preload and of atrial distention as reported by others. This suggests a hyporesponsiveness of the atria to release ANF.

Atrial Natriuretic Factor↗
PubMed1988

Ganglionic immunoreactive atrial natriuretic factor in rat experimental hypertension.

Because previous data have suggested a dependence of ganglionic atrial natriuretic factor (ANF) content on preganglionic cholinergic input, we investigated the possibility that the increased neural activity observed in spontaneously hypertensive rats (SHR) may be reflected by ganglionic immunoreactive ANF levels. Four-week-old normotensive SHR had celiac ganglionic immunoreactive ANF values comparable to those of Wistar-Kyoto rats (WKY). When they became hypertensive, however, at 12 weeks of age, the SHR manifested higher immunoreactive ANF levels in celiac ganglia than the WKY group (25.3 +/- 2.6 vs 14.5 +/- 1.7 pg/ganglion; p less than 0.01), but there were no differences in levels in the superior cervical and nodose ganglia. The values in celiac ganglia were quadrupled on the average in hypertensive Dahl salt-sensitive rats under the influence of an 8% salt intake for 5 weeks, but no difference was noted in any of these ganglia between this group and their salt-resistant partners. The celiac and superior cervical ganglionic immunoreactive ANF content in normotensive Sprague-Dawley rats was higher with high salt than with normal salt intake. Hypertensive rats treated with deoxycorticosterone acetate (DOCA)-salt and sham-treated controls showed immunoreactive ANF concentrations in celiac ganglia similar to those detected in Dahl rats but, again, no differences were found between groups. Thus, hypertensive SHR, compared to WKY, have higher celiac ganglionic immunoreactive ANF levels, unlike Dahl salt-sensitive and DOCA-salt animals relative to their respective controls. This increase is unique to SHR (although all three models have elevated plasma immunoreactive ANF when they are hypertensive) and to the celiac ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

ANF in experimental congestive heart failure.

The plasma and cardiac levels of immunoreactive (IR) atrial natriuretic factor (ANF) were measured during the entire lifespan of cardiomyopathic hamsters, which eventually develop spontaneous congestive heart failure, and were correlated with immunohistochemical, ultrastructural, and immunocytochemical changes in the secretory apparatus of atrial and ventricular cardiocytes. Plasma IR-ANF rose in the early stages of the disease, reached a maximum in moderate heart failure, and declined thereafter but remained above control values. The peptide decreased constantly in the atria during the evolution of the disease but increased markedly in the ventricles. Its highest levels were found in the inner half of the left ventricle. In atrial cardiocytes, the size and complexity of the Golgi complex increased with the progression of the disease, whereas the number, size, and IR-ANF content (as assessed by the immunogold technique) of secretory granules decreased constantly. In ventricular cardiocytes, the size of the Golgi complex increased, and typical secretory granules were present in approximately 20% of these cells, regardless of their localization in the myocardium. The results suggest that stimulation of ANF secretion in atrial cardiocytes leads to a dissociation between synthesis and release, the latter being maximal according to ultrastructural and immunocytochemical criteria. In ventricular cardiocytes, the same stimulation culminates in increased synthesis and the possibility of release via two pathways: one constitutive, the other regulated. Thus, the elevated plasma levels of IR-ANF in congestive heart failure may be derived from secretion by both atrial and ventricular cardiocytes.

Animals↗
PubMed1988

[Effects of phenylephrine on atrial natriuretic factor and the renin-aldosterone axis in normal patients and essential hypertensive patients].

Phenylephrine infusions enhance diuresis and natriuresis both in normal subjects and patients with essential hypertension, whereas they have an opposite effect on urinary aldosterone excretion, decreasing it in normal subjects and enhancing it in hypertensive patients. With the new knowledge concerning the atrial natriuretic factor (ANF), it seemed a strong possibility that in normal subjects phenylephrine infusions should exert its effect through the increased release of ANF, as suggested by in vitro studies. Phenylephrine infusions at high pressor dose (to increase diastolic pressure by 25 mmHg) in six healthy volunteers increased plasma ANF and cGMP and decreased plasma renin activity and aldosterone concentrations. Urinary volume, sodium, and cGMP excretion were also increased. Phenylephrine infusions at low pressor dose (to increase diastolic pressure by 12-15 mmHg), in healthy subjects and in five patients with mild essential hypertension, significantly increased plasma ANF concentrations and decreased plasma renin activity to the same degree in both groups. But, whereas in normal subjects plasma aldosterone decreased significantly, it increased in patients with mild essential hypertension despite the simultaneous rise in plasma ANF concentration.

Adult↗
PubMed1988

Atrial natriuretic factor: response to cardiac operation.

Patients who undergo cardiopulmonary bypass experience derangements of complement activation, prostaglandin metabolism, and catecholamine secretion, which have all been posited to explain postoperative fluid retention and paroxysmal hypertension. Atrial natriuretic factor, a hormonal peptide released by the cardiac atria, regulates vascular volume by increasing sodium excretion and decreasing vasomotor tone and catecholamine synthesis. We examined its possible response to cardiopulmonary bypass in 23 patients (18 having cardiopulmonary bypass and, as a control group, five having thoracotomy) who underwent serial blood sampling to measure plasma atrial natriuretic factor levels before, during, and after operation. Thoracotomy alone had no effect on atrial natriuretic factor levels before, during, and after operation. Patients with cardiac valve lesions who had a higher incidence of arrhythmias and congestive heart failure showed elevated preoperative atrial natriuretic factor values (p less than 0.05). Normally, atrial natriuretic factor release is directly related to atrial filling pressure, but all patients having cardiopulmonary bypass revealed a paradoxical rise of atrial natriuretic factor during cardiopulmonary bypass (p less than 0.01) and a lack of correlation between atrial filling pressure and atrial natriuretic factor secretion in the early postoperative period. The atrial natriuretic factor response to pulmonary wedge pressure began to normalize 24 hours after operation. The unique reaction of this recently discovered cardiac hormone to cardiopulmonary bypass suggests its possible role in the pathophysiologic response to cardiac operation.

Atrial Natriuretic Factor↗
PubMed1988

Ganglionic, spinal cord and hypothalamic atrial natriuretic factor: its distribution, origin and possible role in spontaneously hypertensive rats.

We report the occurrence of the atrial natriuretic factor (ANF) prohormone in the hypothalamus, spinal cord and sympathetic ganglia determined by measurement of immunoreactive ANF by two peptide-specific radio-immunoassays with antibodies against near-C-terminal and near-N-terminal portions of ANF prohormone. This suggests local ANF generation in neural structures. In spontaneously hypertensive rats (SHR) we found an elevated ANF-C content in all tissues along the pathway of increased efferent sympathetic outflow, which is present in this animal model. The ANF-N was augmented in SHR only in the hypothalamus. This indicates an overall increase of neural ANF in SHR. The reported neuroinhibitory function of increased neural ANF, however, was attenuated by a decrease in the number of some brain and peripheral ganglionic ANF binding sites in SHR. It remains to be determined whether the increased neural ANF in SHR is a primary phenomenon or a compensatory increase induced by high blood pressure.

Animals↗
PubMed1988

Effect of nitroglycerin on left ventricular hydraulic load.

It has previously been shown that nitroglycerin increases the compliance of forearm arteries. The present study investigates whether nitroglycerin reduces the hydraulic load on the heart (as measured by aortic input impedance) by a mechanism compatible with an increase in peripheral arterial compliance. In eight subjects, measurements of aortic flow and pressure were made with a catheter tipped probe before and during intravenous nitroglycerin (6 to 30 micrograms/min) administration. The reduction of aortic systolic pressure (129 +/- 5 to 113 +/- 4 mmHg, P less than 0.001) was due to a decrease in the late systolic pressure peak. There was no change in stroke volume, heart rate or systemic vascular resistance. The lower systolic pressure resulted from a decrease in the amplitude of the first harmonic of input impedance (210 +/- 19 to 143 +/- 11 dyne.s.cm-5, P less than 0.005) yet characteristic impedance (a measure of local aortic distensibility) did not change. The ratio of maxima to minima of the impedance spectrum was reduced (1.02 +/- 0.09 to 0.71 +/- 0.11, P less than 0.05) suggesting a decrease in the amplitude of reflected waves contributing to aortic impedance. Nitroglycerin at doses which have no effect on arteriolar resistance vessels, reduces systolic aortic pressure by diminishing the amplitude of wave reflections returning to the ascending aorta in late systole. This mechanism is compatible with the peripheral arterial effects of nitroglycerin.

Hemodynamics↗
PubMed1987

Catecholamine, dopamine-beta-hydroxylase and atrial natriuretic factor content in separate heart chambers of cardiomyopathic hamsters.

Since previous investigations have suggested a relationship between atrial natriuretic factor (ANF) and dopamine-beta-hydroxylation, cardiomyopathic hamsters were studied for atrial and ventricular catecholamine (CA) and dopamine-beta-hydroxylase (D beta H) content as correlates to a parallel finding of markedly decreased atrial but increased ventricular ANF concentrations in these animals. It was noted that, with progressive cardiomyopathy, the reduced tissue norepinephrine (NE) content paralleled the declining D beta H activity in the atria. In the ventricles, however, the progressively-decreasing NE content was associated with an increase of D beta H. These data indicate that the NE depletion is mediated by different mechanisms in the ventricles and atria. They do not support a simple relationship between NE depletion and tissue D beta H activity or between the latter and tissue ANF concentrations.

Animals↗
PubMed1987

Opposite effects of neuropeptide Y (NPY) and polypeptide YY (PYY) on plasma immunoreactive atrial natriuretic factor (IR-ANF) in rats.

Female Sprague-Dawley rats were administered NPY and PYY in doses of 0.1, 2.5 or 5, and 10 micrograms in order to determine whether the natriuretic action is the result of increased ANF secretion. NPY injection increased significantly IR-ANF while PYY decreased IR-ANF in the dose-response manner in normally-hydrated rats as well as in water-loaded rats. Opposite effects on plasma IR-ANF were exerted by NPY and PYY, indicating that an increase of ANF release may be responsible for NPY-induced natriuresis.

Animals↗
PubMed1987

Atrial natriuretic factor partially inhibits the stimulated catecholamine synthesis in superior cervical ganglia of the rat.

We examined whether the atrial natriuretic factor (ANF) may affect the function of the peripheral autonomic neurons. ANF was found to inhibit the carbachol-stimulated synthesis of catecholamines from their labelled [3H]tyrosine precursor in an organ suspension of the rat superior cervical ganglia in vitro. This is compatible with the possibility that the previously observed inhibitory action of ANF on sympathetic nervous activity and the presence of immunoreactive ANF in the rat peripheral autonomic ganglia is related to an inhibitory-neuromodulatory role of ANF in the process of ganglionic neurotransmission.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Plasma atrial natriuretic factor concentrations in essential and renovascular hypertension.

Plasma atrial natriuretic factor concentrations were measured in 44 patients with mild untreated essential hypertension and 48 normotensive controls. Mean venous plasma atrial natriuretic factor concentrations were 13.2 (SEM 1.5) and 13.0 (1.3) ng/l in the hypertensive patients and controls, respectively. Plasma atrial natriuretic factor concentrations were significantly correlated with age in both groups. Plasma atrial natriuretic factor concentrations were also measured during renal vein catheterisation in a group of 15 hypertensive patients; of these, eight had renovascular hypertension, and in all eight cases plasma atrial natriuretic factor concentrations were increased in the aorta and inferior vena cava. It is concluded that mild essential hypertension is not associated with increased plasma atrial natriuretic factor concentrations, whereas an age related increase in concentrations occurs in hypertensive and normotensive people.

Adult↗
PubMed1987

Plasma immunoreactive atrial natriuretic factor is inhibited by selective blockade of alpha 2-adrenergic receptors in conscious Sprague-Dawley rats.

Effects of alpha 2-adrenergic receptors and calcium channel blockade on basal and clonidine-stimulated immunoreactive atrial natriuretic factor (IR-ANF) in conscious Sprague-Dawley rats were evaluated. Clonidine was injected intravenously (i.v.) in a dose of 50 micrograms. Yohimbine and verapamil were used as a pretreatment, with clonidine in a dose of 50 micrograms and 0.5 mg respectively. The effects of yohimbine (1, 20, 50 micrograms) and verapamil (0.5 mg) on basal IR-ANF were also studied. Plasma IR-ANF was measured by radioimmunoassay with prior extraction on heat-activated Vycor glass. Clonidine injection in a dose of 50 micrograms caused a marked increase of plasma IR-ANF from 34.0 +/- 7.0 pg/ml (mean +/- S.E.M.) to 457.1 +/- 66.3 pg/ml. Clonidine-stimulated ANF secretion was partially inhibited by yohimbine from 457.1 +/- 66.3 pg/ml (mean +/- S.E.M.) to 99.9 +/- 23.1 pg/ml. Moreover, yohimbine in highest doses (50 micrograms) decreased the basal plasma IR-ANF from 34.0 +/- 7.0 pg/ml (means +/- S.E.M.) to 6.8 +/- 3.6 pg/ml. Verapamil did not alter basal and clonidine stimulated IR-ANF. These results indicate the important role played by alpha 2-adrenergic receptors in mediating ANF release.

Animals↗
PubMed1987

An emerging relationship between peripheral sympathetic nervous activity and atrial natriuretic factor.

The sympathetic nervous system and atrial natriuretic factor (ANF) are intimately involved in sodium, volume and blood pressure homeostasis, particularly in response to volume and pressure overloads. Although rapid progress in this field indicates several levels of interaction between both systems, the role of sympathetic nervous activity (SNA) in ANF release remains a controversial topic. There is growing evidence that ANF is an inhibitory modulator of sympathetic outflow (which in turn, may contribute to ANF's effect) and, vice-versa, SNA attenuates the target actions of ANF. Compensatory sympathetic reactions to changes induced by ANF may also have an overriding influence on its target actions. Dopamine appears to play a special role in these interactions. It is not only a precursor of norepinephrine but probably fulfills an independent function in the regulation of salt balance, similar in many respects to that of ANF.

Animals↗
PubMed1987

Release of immunoreactive atrial natriuretic factor from the isolated perfused rat lung.

The secretion of ANF by the rat lung was demonstrated in the present study. Four forms of immunoreactive ANF were detected in rat lung homogenates, including the 126 amino acid prohormone but only a low molecular mass peptide was released during lung perfusion. The released ANF inhibited forskolin-stimulated aldosterone secretion from rat zona glomerulosa cell suspensions, and this biological effect was comparable to that of the synthetic C-terminal part of the prohormone (Arg-101-Tyr-126).

Aldosterone↗