Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “atrial function”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed1997

Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation.

BACKGROUND: Recently, we developed a goat model of chronic atrial fibrillation (AF). Due to AF, the atrial effective refractory period (AERP) shortened and its physiological rate adaptation inversed, whereas the rate and stability of AF increased. The goal of the present study was to evaluate the role of (1) the autonomic nervous system, (2) ischemia, (3) stretch, (4) atrial natriuretic factor (ANF), and (5) rapid atrial pacing in this process of electrical remodeling. METHODS AND RESULTS: Twenty-five goats were chronically instrumented with multiple epicardial atrial electrodes. Infusion of atropine (1.0 mg/kg; n=6) or propranolol (0.6 mg/kg; n=6) did not abolish the AF-induced shortening of AERP or interval (AFI). Blockade of K+(ATP) channels by glibenclamide (10 micromol/kg; n=6) slightly increased the AFI from 95+/-4 to 101+/-5 ms, but AFI remained considerably shorter than during acute AF (145 ms). Glibenclamide had no significant effect on AERP after electrical cardioversion of AF (69+/-14 versus 75+/-15 ms). Volume loading by 0.5 to 1.0 L of Hemaccel (n=12) did not shorten AERP. The median plasma level of ANF increased from 42 to 99 pg/mL after 1 to 4 weeks of AF (n=6), but ANF infusion (0.1 to 3.1 microg/min, n=4) did not shorten AERP. Rapid atrial pacing (24 to 48 hours; n=10) progressively shortened AERP from 134+/-10 to 105+/-6 ms and inversed its physiological rate adaptation. CONCLUSIONS: Electrical remodeling by AF is not mediated by changes in autonomic tone, ischemia, stretch, or ANF. The high rate of electrical activation itself provides the stimulus for the AF-induced changes in AERP.

Animals↗
PubMed2005

Adenosine-stimulated atrial natriuretic peptide release through A1 receptor subtype.

Adenosine acts as an important protector of ischemic myocardium through coronary vasodilation and the depression of cardiac contractility. The protective effect of adenosine may partly relate to the cardiac hormone atrial natriuretic peptide (ANP). The aim of the present study was to investigate the effects of adenosine and the adenosine receptor subtype on atrial hemodynamics and ANP release using isolated perfused beating rat atria. Adenosine, a nonselective adenosine receptor agonist, increased the ANP release with negative inotropism in a dose-dependent manner. Adenosine-stimulated ANP release was attenuated by a selective A1 antagonist but not A(2A) antagonist or A3 antagonist. The order of potency of the various agonists for the ANP release was A1 agonists>>A3 agonist=adenosine>A(2A) agonist. The order of potency for the negative inotropy was A1 agonists>adenosine=A(2A) agonist>A3 agonist. The negative inotropism and ANP release by a specific A1 agonist (N6-cyclopentyl-adenosine) were also attenuated by A1 antagonist but not A(2A) antagonist or A3 antagonist. Treatment with A1 agonist resulted in a decrease of cAMP contents in atria and perfusates. The agonist-stimulated ANP release was significantly attenuated in the presence of forskolin, isoproterenol 8-Br-cAMP, or an adenylyl cyclase inhibitor. These results suggest that the A1 receptor subtype is responsible for the adenosine-induced ANP release and negative inotropism through adenylyl cyclase-cAMP pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

The heart as an endocrine gland.

The sequence of atrial natriuretic factor (ANF) has been determined, as well as the complete structure of the rat and human complementary DNA and gene. ANF and ANF messenger RNA are present not only in atria but also in ventricles. The circulating form of ANF has been identified as the C-terminal of the molecule, ANF (Ser 99-Tyr 126). The isolated secretory granules of rat atrial cardiocytes contain only pro-ANF (Asn 1-Tyr 126). An enzyme (IRCM-SP1) has been isolated from heart atria and ventricles. This enzyme is highly specific in cleaving ANF (Asn 1-Tyr 126), to yield ANF (103-126), (102-126), and (99-126). In target cells, ANF produces a rise in cyclic guanosine 3',5'-monophosphate (cGMP) due to activation of particulate guanylate cyclase, and inhibition of adenylate cyclase leading in some cases to a decrease in cyclic adenosine 3',5'-monophosphate (cAMP). ANF produces relaxation of rabbit and rat aortic strips, inhibits steroidogenesis in both zona glomerulosa and zona fasciculata cells, and inhibits the release of arginine vasopressin from the isolated rat hypothalamohypophysial preparation in vitro but decreases AVP release in vivo only at pharmacological doses. In all forms of experimental hypertension, plasma levels of ANF are increased and, at some time periods, atrial levels are also decreased. The ventricular levels of immunoreactive ANF are also increased in renal hypertension. Infusion of ANF by minipumps decreases the blood pressure near control levels in several models of experimental hypertension. In cardiomyopathic hamsters with heart failure, the atrial levels of immunoreactive ANF are decreased while the plasma and ventricular levels are increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Calcium dependency of frequency-stimulated atrial natriuretic peptide secretion.

In this study we examined the mechanism whereby atrial natriuretic peptide secretion is increased when the frequency of contraction is raised from 2 to 5 Hz. We tested the hypothesis that calcium plays a significant role in the frequency-stimulated response. Using superfused rat left atria, we found that lowering the superfusate calcium concentration from 1.8 to 0.2 mmol/L abolished the frequency-stimulated atrial natriuretic peptide secretory response. Superfusion with ryanodine (1 mumol/L), an inhibitor of sarcoplasmic reticulum calcium release, resulted in a minimal inhibitory effect. Superfusion with 50 mumol/L nitrendipine or 10 mumol/L diltiazem inhibited the frequency-stimulated response by 46% to 48%. The lack of total inhibition suggested that an additional mechanism of calcium influx was involved, namely, inward calcium movement carried by Na(+)-Ca2+ exchange. As intracellular sodium has been reported to rise with an increase in beat frequency, a fall in the sodium gradient would favor inward calcium movement by Na(+)-Ca2+ exchange. Because we could not directly assess the role of Na(+)-Ca2+ exchange in this experimental paradigm, we examined the effect of lowering the transmembrane sodium gradient on atrial natriuretic peptide secretion by superfusion with the sodium channel activator veratridine or the sodium ionophore monensin. Superfusion with 1 mumol/L veratridine increased atrial natriuretic peptide secretion by 2.3-fold, and 1, 5, and 10 mumol/L monensin increased secretion by 1.1-, 2.1-, and 15.7-fold, respectively. In addition, we examined the possibility that the reported rise in intracellular sodium associated with increased beat frequency was due to enhanced Na(+)-H+ antiporter activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

Quantification of human atrioventricular nodal concealed conduction utilizing S1S2S3 stimulation.

We studied antegrade concealed conduction of atrial extrastimuli (A2) that blocked in the atrioventricular (AV) node in eight subjects, using a third extrastimulus (A3), coupled at decreasing coupling intervals to A2. Three A1-A2 intervals were tested in each subject: late (just shorter than AV nodal effective refractory period), intermediate, and early (just longer than atrial functional refractory period). The curves relating the following variables were constructed for each A2: A1-A3, H1-H3 and A2-A3, A3-H3. The former was compared to the control A1-A2, H1-H2 curve. Concealment of A2 was demonstrated in all eight subjects at the three tested values of A1-A2. The A2-A3, A3-H3 curve allowed analysis of AV nodal conduction time (A3-H3) and AV nodal recovery time (defined as the shortest A2-A3 at which the impulse conducted to the His bundle) at identical values of A2-A3. In all subjects the timing of blocked A2 had minimal effect on both AV nodal conduction time and recovery time. In five of the eight subjects a late A2 sporadically conducted to the His bundle. Conduction of A2 to the His bundle resulted in marked lengthening of both AV nodal conduction and recovery times. Concealed conduction of A2 was always demonstrated, but the degree of concealment was relatively fixed, whether A2 was an early, intermediate, or late blocked premature beat. Slow conduction of A2 had a much greater effect than concealment of A2 on subsequent impulse conduction.

Aged↗
PubMed1986

George E. Brown memorial lecture. Role of atrial peptides in body fluid homeostasis.

Extracts of mammalian atria, but not ventricles, induce marked diuresis, natriuresis, and reduction in blood pressure when infused systemically in rats and dogs. These extracts also inhibit aldosterone biosynthesis and renal renin release. Natriuretic peptides, 21 amino acids and longer, have been isolated from atria of rodents and man, and share a nearly homologous amino acid sequence at the carboxyterminus. Natriuretic activity resides in a 17-amino acid ring formed by a disulfide bridge, and the C-terminal Phe-Arg appears necessary for full biological potency. The deoxyribonucleic acid-encoding atrial natriuretic peptides have been cloned and the gene structure elucidated. Reduction of the diuretic and natriuretic responses to an acute volume load by right atrial appendectomy first suggested a role for atrial peptides in the physiological response to plasma volume expansion. Subsequently, release of peptides with natriuretic and spasmolytic properties from isolated heart preparations in response to right atrial distension was demonstrated by bioassay and radioimmunoassay. The presence of these peptides in normal rat and human plasma in concentrations of 20-100 pM, and the findings of increased levels in response to acute and chronic plasma volume expansion, rapid atrial tachyarrhythmias, systemic hypertension, congestive heart failure, and renal insufficiency imply that they play an important role in body fluid homeostasis. The mechanisms by which atrial peptides increase renal salt and water excretion are as yet unclear. Renal vascular effects have been consistently demonstrated, and limited evidence for direct actions on tubule ion transport has also been reported recently. In vitro, these peptides cause precontracted vascular and nonvascular smooth muscle to relax, mediated by a direct action on smooth muscle cells. Specific receptors for these peptides have been characterized in crude membranes prepared from whole kidney homogenates and adrenal glomerulosa cells, in intact glomeruli and cultured glomerular mesangial cells, and in intact bovine aortic smooth muscle and endothelial cells. Natriuretic peptides stimulate cyclic guanosine monophosphate accumulation in target tissues, and augment particulate guanylate cyclase activity in membrane fractions, suggesting that cyclic guanosine monophosphate is the second messenger mediating their cellular action.

Aldosterone↗
PubMed1987

Role of right and left atria in natriuresis and atrial natriuretic factor release during blood volume changes in the conscious rat.

This study investigated whether excision of either the right or left atrial appendage of rats alters their natriuretic response and the release of atrial natriuretic factor during acute blood volume expansion or reduction. These animals were subjected to a thoracotomy and either had their right or left atrial appendages removed or underwent a right or left atrial sham appendectomy for comparative, control purposes. Intrajugular vein, intracarotid artery, and intravesical catheters were installed 3-4 weeks later under sodium pentobarbital anesthesia. Then, when the rats were conscious, blood volume was expanded using blood from donor rats once every 15 minutes in 3 increments of 10% of the calculated total blood volume at a rate of 5 ml/kg/min. Blood and urine samples were collected before volume expansion and at the end of each 15-minute period, with the withdrawn blood being replaced. A maximal fourfold increase in urinary volume, urinary sodium excretion, and plasma atrial natriuretic factor was observed in all but the right-atrial-appendectomized animals. Plasma atrial natriuretic factor, urinary volume, and urinary sodium excretion were correlated in all 4 groups. No significant changes in blood pressure or hematocrit were noted. Plasma vasopressin, measured at the end of volume expansion, was significantly lower in animals subjected to left atrial appendectomy. High-performance liquid chromatography of plasma from the control groups indicated that most of the released ANF during blood volume expansion corresponded to a high molecular weight peptide. Additional rats, processed as above, were subjected to 10% blood volume decrements.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor.

The current studies were designed to investigate the mechanisms in the intact anesthetized dog that control the release of atrial natriuretic factor (ANF). In vitro, mechanical stretch of atrial tissue produces an increased release of ANF. In vivo, changes in atrial pressure correlate positively with circulating ANF levels. The present investigations used 6 open-chest anesthetized dogs to evaluate the role of atrial pressure versus atrial stretch, the latter determined by atrial transmural pressure, in the release of ANF. In a paired design, animals underwent cardiac tamponade followed by constriction of the aorta and pulmonary artery. Tamponade produces a balanced increase in intra-atrial and pericardial pressures. Thus, despite an elevated atrial pressure, there is no increase in transmural pressure producing atrial stretch. Great artery constriction increases intra-atrial but not pericardial pressure, resulting in an increase in atrial transmural pressure and atrial stretch. Cardiac tamponade increased right atrial pressure (0.8 +/- 0.3 to G.6 +/- 0.6 mm Hg, p less than 0.001) and pulmonary capillary wedge pressure (3.7 +/- 0.6 to 8.8 +/- 0.6 mm Hg, P less than 0.001). Constriction of the aorta and pulmonary artery also increased right atrial pressure (1.5 +/- 0.8 to 6.3 +/- 0.8 mm Hg, p less than 0.05) and pulmonary capillary wedge pressure (4.6 +/- 0.3 to 7.8 +/- 1.0 mm Hg, p less than 0.05). Atrial transmural pressure increased only during great artery constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Pressor hormones regulate atrial-stretch-induced release of atrial natriuretic peptide in the pithed rat.

Atrial wall stretching is a known stimulus for atrial natriuretic peptide (ANP) secretion. The effects of the stimulation of autonomic nervous system, hemodynamic factors, and humoral factors (epinephrine, angiotensin, vasopressin, and brain extracts) on the release of ANP under basal conditions and during increased atrial pressure produced by acute volume loading in pithed rats were examined. In conscious rats, acute volume expansion by 0.9% of saline (4 ml) increased the plasma immunoreactive ANP (IR-ANP) concentrations by a factor of 4 (140 +/- 30 pg/ml vs. 521 +/- 140 pg/ml, p less than 0.001, n = 8), whereas volume-induced ANP release was blocked in pithed rats (75 +/- 9 pg/ml vs. 99 +/- 13 pg/ml, NS, n = 7). The ANP versus right atrial pressure curve shifted to the right, indicating that much smaller amounts of IR-ANP were released in pithed than in conscious rats for each given increase in right atrial pressure. Electrical vagal and sympathetic nerve stimulation or changes in heart rate had no effect on plasma IR-ANP concentrations and failed to restore the volume-load-induced release of ANP in pithed rats. When extracts of anterior pituitary lobe, brain cortex, or hypothalamus were infused, no effect on volume-expansion-induced plasma IR-ANP levels was seen. In contrast, acute volume expansion caused a fourfold increase in levels of circulating IR-ANP in pithed rats that received posterior pituitary extracts, and the ANP versus right atrial pressure curve shifted markedly to the left. Infusion of a V1 antagonist blocked the volume-expansion-induced ANP release produced by the posterior pituitary extract. When [Arg8]-vasopressin (0.025 or 0.05 micrograms/kg/min) was infused to pithed rats, mean arterial pressure increased but basal plasma IR-ANP did not change significantly. However, acute volume expansion in the presence of vasopressin infusion (0.05 micrograms/kg/min) increased the amount of circulating IR-ANP by a factor of 4 (113 +/- 14 pg/ml vs. 414 +/- 43 pg/ml, p less than 0.001, n = 8). Thus, for a given increase in right atrial pressure, a similar amount of IR-ANP was released in the pithed rat during the vasopressin infusion as in the normal conscious animal. V1 antagonist blocked the increase in mean aterial pressure as well as the increase of plasma IR-ANP produced by [Arg8]-vasopressin. In addition, volume expansion during intravenous epinephrine (1.75 micrograms/kg/min) and angiotensin (1.0 micrograms/kg/min) doubled plasma IR-ANP levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Chronotropic stimulation: a primary effector for release of atrial natriuretic factor.

Release of atrial natriuretic factor (ANF) following an elevation in heart rate is thought to be mediated primarily by a change in atrial stretch. To evaluate the direct effect of chronotropic stimulation on ANF release, isolated rat left atria were electrically paced (1-9 Hz) at constant resting tension (0.5-4 g), and the amount of immunoreactive ANF (IRANF) released at each frequency and tension was quantitated with a sensitive radioimmunoassay. Our results show that at controlled resting tensions greater than 1 g, chronotropic stimulation increased IRANF secretion in a manner dependent on the pacing frequency; rapid atrial rates (e.g., 8 and 9 Hz) were necessary to release ANF at tensions of 1 g or less. Resting tension influenced the magnitude of the secretory response to electrical stimulation. Release of IRANF with contraction frequency was transient in nature and, at high frequencies, was associated with a decrease in developed (systolic) tension in accordance with the negative force-frequency relation inherent in the rat heart. When evaluated at a single diastolic tension and pacing frequency, IRANF release was positively correlated with systolic tension. ANF released under in vitro conditions was approximately 3,000 Da, in agreement with the size of the physiologically circulating form. In atria from reserpinized rats, evidence for involvement of catecholamines in chronotropic-stimulated ANF release was suggested. The presence of lidocaine (5 x 10(-4) M) had no effect on rate-induced ANF secretion. Therefore, chronotropic stimulation releases ANF independently of changes in atrial stretch. The magnitude of this response depends on a combination of pacing frequency and diastolic tension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

cGMP and atrial natriuretic factor regulate cell volume of rabbit atrial myocytes.

Atrial natriuretic factor (ANF) reduces the volume of atrial myocytes by inhibiting Na+/K+/2Cl- cotransport. We determined the role of cGMP and cAMP in ANF-induced shrinkage by using digital video microscopy to measure cell volume; volumes are reported relative to control. ANF (1 mumol/L) reversibly reduced atrial cell volume from 1.0 to 0.915 +/- 0.005 (mean +/- SEM). This effect was mimicked by 10 mumol/L 8-bromo-cGMP (8-Br-cGMP), which decreased myocyte volume to 0.894 +/- 0.007 with an ED50 of 0.99 +/- 0.05 mumol/L. In contrast, 100 mumol/L 8-bromo-cAMP (8-Br-cAMP) did not affect volume, and activating the cAMP pathway with 100 mumol/L 8-Br-cAMP did not alter the volume decrease caused by 8-Br-cGMP or ANF. Inhibition of Na+/K+/2Cl- cotransport with bumetanide (1 mumol/L) also reduced cell volume and prevented further shrinkage on subsequent exposure to 8-Br-cGMP. Similarly, 8-Br-cGMP (10 mumol/L) prevented further shrinkage by ANF. Block of Na(+)-H+ exchange, a participant in volume regulation in other cells, did not alter the response to 8-Br-cGMP. More evidence implicating cGMP was obtained by altering its metabolism. LY83583 (10 mumol/L), a guanylate cyclase inhibitor, blocked ANF-induced cell shrinkage. Zaprinast (100 mumol/L), a cGMP-specific phosphodiesterase inhibitor, markedly potentiated the effect of a threshold concentration of ANF (0.01 mumol/L). The actions of ANF, LY83583, and zaprinast on cGMP levels were verified by radioimmunoassay. These data strongly support the idea that the cGMP cascade is the intracellular signaling pathway responsible for ANF-induced atrial cell shrinkage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Pre-clinical and clinical experience of telmisartan in cardiac remodelling.

Epidemiological studies have established that left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular and cerebrovascular morbidity and mortality. In turn, hypertension is a well-established risk factor for LVH. Ambulatory blood pressure monitoring has shown that 24-h mean ambulatory blood pressure is a particularly powerful predictor of LVH, being superior to casual clinic blood pressure measurements. The magnitude of the rise in blood pressure in the early morning correlates with the extent of LVH. Prospective studies have shown the advantageous effects of antihypertensive therapy on LVH in terms of regression of left ventricular mass (LVM) and subsequent reduction in overt cardiovascular disease. Meta-analysis has identified differences in the ability of different classes of anti-hypertensive agents to bring about regression of LVH, with agents that target the renin angiotensin system (RAS) appearing superior to other agents, such as beta-blockers and diuretics. The distinct pharmacological features of telmisartan suggest that it may be a suitable agent for managing hypertensive patients because it provides sustained control of blood pressure and appears to be very effective in reversing cardiac remodelling. Pre-clinical evaluation has demonstrated that telmisartan suppresses angiotensin II-induced collagen production and secretion by cultured fibroblasts, and reduces left ventricular weight in different animal models. Several clinical studies have demonstrated that, as well as reducing blood pressure (including 24-h mean ambulatory values), telmisartan brings about LVM regression in patients with hypertension, and improves left ventricular and left atrial function. Comparative studies have shown telmisartan's superiority compared with both hydrochlorothiazide and carvedilol in regressing LVM, the additional activity probably being explained by the sustained blood pressure control and the non-haemodynamic effects of targeting the RAS. The ultimate proof of the clinical value of telmisartan will be provided by the outcome trials ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) currently being conducted in high-risk patients.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2003

Stretch-activated atrial natriuretic peptide secretion in atria with heat shock protein 70 overexpression.

The mechanical overload of the heart is known to induce the expression of atrial natriuretic peptide (ANP) and heat-shock protein 70 (HSP70) in the heart. However, the relationship between these two substances remains unknown. In the present study, we characterized ANP secretion from mouse atria and examined a possible role that HSP70 may play in the regulation of ANP synthesis and secretion by using atria in transgenic mice in which HSP70 was overexpressed. We generated transgenic mice harboring the human HSP70gene under the transcriptional control of human myosin heavy-chain promoter. In these mice, the transgene was overexpressed in the heart. Both atrial ANP messenger RNA and its concentration in the HSP70 transgenic mice were measured; these were not significantly different from those in wild-type mice. In isolated perfused nonbeating atria, basal secretion of ANP was similar in both groups. When atrial volume was increased by changing atrial pressure, extracellular fluid (ECF) translocation and ANP secretion proportionately increased. Changes in atrial volume and ECF translocation and ANP secretion were positively correlated. However, these parameters did not significantly differ between the two groups. Endothelin-1 (ET-1), the strongest paracrine stimulus of ANP secretion, accentuated stretch-activated ANP secretion without significantly changing mechanically stimulated ECF translocation, as compared with that in the wild-type mice. The increased ANP secretion due to ET-1 in the transgenic mice was similar to that in the wild-type mice. The results suggest that both atrial stretching and ET-1 are important stimuli to ANP secretion from mouse atria, and the responsiveness of the ANP system to those stimuli are unlikely coupled to the pathway involving HSP70.

Animals↗
PubMed2004

Different responses of atrial natriuretic peptide secretion and its receptor density to salt intake in rats.

This study investigated whether high-salt intake influences atrial natriuretic peptide (ANP) system, atrial content, and release rate of ANP as well as receptor density in the kidney were measured in salt intake rats. Male Sprague-Dawley rats received either 0.9% or 2% salt in their drinking water for 10 days. The stretch-induced ANP secretion from isolated perfused non-beating left atria was accentuated, and the production of cGMP by ANP in renal cortical tissue membranes were pronounced in rats exposed to 0.9% salt for 10 days but not in rats exposed to 2% salt. The levels of ANP receptor density and expression in renal cortex were decreased in 2% salt intake rats but not in 0.9% salt intake rats. No significant differences in atrial and plasma concentrations of ANP and water balance were observed in both salt intakes. Therefore, these results suggest that atrial ANP secretion and its binding sites in the kidney may respond differently to ingested salt concentrations in rats.

Animals↗
PubMed1985

The heart and the atrial natriuretic factor.

The search for natriuretic hormones or factors by studies of negative pressure breathing, atrial distension experiments, head-out water immersion, expansion of blood volume, Na+/K+-ATPase inhibitors and parabiosis experiments in Dahl rats has led to the finding that the atria are a peptide-secreting endocrine gland. This new natriuretic hormone has now been purified, sequenced and synthetized, and its cDNA and gene have been cloned. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex, and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure, and expansion of blood volume are beginning to emerge.

Adrenal Glands↗
PubMed1993

Stretch-induced atrial natriuretic factor release utilizes a rapidly depleting pool of newly synthesized hormone.

Atrial muscle stretch is widely believed to be the main stimulus for atrial natriuretic factor (ANF) release. However, a few reports have shown that although stretch induces an immediate increase in ANF output, this release rapidly decays even though hormone stores are not significantly depleted. In the present work, this phenomenon was studied in an isolated rat atria preparation using double isotope labeling. The tissue was labeled with [14C]leucine for 3 h followed by a 1-h chase, and then with [3H]leucine for 1 h. A final 1-h chase period was conducted with the tissue under basal (0.2-g load) or stretched (5-g load) conditions. During this final chase period, the [14C]ANF represented older, stored ANF and the [3H]ANF represented the newly synthesized peptide. After both the [14C]- and [3H]leucine pulses, immunoprecipitable isotope incorporated into ANF appeared in the chase medium within the first 10 min and stabilized to lower levels after 20 min of chase. Stretch resulted in an immediate significant increase in immunoreactive ANF release and a decrease in the medium [14C]ANF specific activity (SA). However, no change was observed in the medium [3H]ANF SA but the tissue SA tended to decrease. It is concluded that a portion of ANF is immediately and preferentially released upon synthesis, while the remainder is taken up into tissue stores and released from them at a lower rate. The secretory response to stretch was demonstrated to consist of a rapid, short-lived burst of newly synthesized ANF, suggesting an increased translocation of newly synthesized hormone into a stretch-sensitive, rapidly depletable pool. Given the nature of this pool, additional factors yet to be characterized likely come into play to maintain chronically elevated circulating levels of ANF.

Animals↗
PubMed1993

Atrial stretch induces rapid increase in brain natriuretic peptide but not in atrial natriuretic peptide gene expression in vitro.

Pressure and volume overload in vivo is characterized by induction of the expression of two cardiac hormones, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), but whether stretch directly or other pathophysiological factors associated with cardiac overload cause the activation of these genes is not known. In the present study we examined the effect of short-term (from 30 min to 2 h) direct myocardial stretch on atrial ANP and BNP synthesis and release in modified perfused rat heart preparation that enabled the stepwise distension of the right atrium by pressures approximating those found in vivo. The increase in right atrial pressure by 3.6 mm Hg for 2 h resulted in a 3.3- (p < 0.001) and 1.7-fold (p < 0.02) increase in the rate of IR-ANP and IR-BNP release, respectively, into the perfusate. The maximal increase in both ANP and BNP release was seen after 20 min distension. Thereafter the perfusate IR-ANP and IR-BNP concentration gradually decreased, reaching control values within 2 hours. Chromatographic analysis showed that the hearts primarily release the active, processed 28- and 45-amino acid ANP- and BNP-like peptides, respectively, both before and during atrial stretch. Atrial stretch induced rapid stimulation of BNP gene expression: 1.9- (p < 0.001) and 4.5-fold (p < 0.001) increase in right auricular BNP mRNA levels after 1.0 and 2.0 hours' stretching, respectively, was found on Northern blot analysis, while no change was seen after 30 min distension. In contrast, stretching for up to 2 h did not change auricular ANP mRNA, IR-ANP or IR-BNP levels. Our results show for the first time that atrial stretch induces rapid stimulation of both synthesis and secretion of BNP. The induction of BNP gene expression in the very early stages of cardiac overload mimics the induction of protooncogenes and occurred without involvement of humoral or neural factors. The lack of response of atrial ANP mRNA levels demonstrates that the regulation of BNP gene expression differs from that of ANP.

Animals↗