Temperature and adrenoceptors in the frog heart

1. Cardiac adrenergic receptors in a frog, Rana tigrina, were examined in winter and summer months using isolated atria preparation maintained at 24 degrees, 14 degrees and 6 degrees C. Treatments included an examination of the atrial responses to selective alpha and beta adrenergic agonists (phenylephrine and isoproterenol respectively) and antagonists (phentolamine and propranolol). 2. Basal atrial beating rates differed between summer and winter months and increased with temperature. 3. Phenylephrine produced dose-dependent increases in the atrial beating rate and tension in the winter frogs only at 6 degrees C. These increases were blunted by phentolamine. 4. Isoproterenol produced positive chronotropic effects of 14 degrees and 24 degrees C but not at 6 degrees C in both summer and winter frogs; these effects were abolished by propranolol. Further, at 6 degrees C, the contractile response of the atrial tissue to isoproterenol was very sensitive. 5. Data suggests that the alpha adrenoceptor might be physiologically important to the frog in the low temperature environment of the cold season, during which period the cardiac beta adrenergic activity would be minimal or even absent.     

Adrenergic-cholinergic interactions in left atria. II. Comparison of the antagonism of inotropic responses to alpha- and beta-adrenoceptor stimulation and BAY K 8644 by carbachol, D-600, and nifedipine

The muscarinic agonist carbachol has previously been shown to reverse positive inotropic responses of rabbit left atrial strips to equiactive doses of the beta-adrenoceptor agonist isoproterenol and to the alpha-adrenoceptor agonist phenylephrine. Responses to phenylephrine were measured in the presence of the beta-blocker timolol. However, carbachol was not able to reverse the increase in tension produced by elevating the extracellular Ca2+ concentration. To gain more information about the nature of the functional interaction of carbachol with alpha- and beta-receptor stimulants in left atria, the interaction of carbachol with these agonists, as well as with elevated Ca2+ and the Ca2+ activator compound BAY K 8644, was compared with that of the Ca2+ antagonists D-600 and nifedipine. The results demonstrate that the Ca2+ antagonists exhibit a selectivity similar to that of carbachol, in that responses to both isoproterenol and phenylephrine plus timolol were blocked by low concentrations of D-600 and nifedipine, which had no effect on positive inotropic responses to elevated Ca2+. Higher concentrations of these antagonists shifted the Ca2+ dose-response curve to the right. In addition, although phenylephrine and BAY K 8644 increased tension to a similar extent, responses to phenylephrine were more sensitive than responses to BAY K 8644 to inhibition by both carbachol and D-600. These similarities between the effects of low concentrations of D-600 and nifedipine and those of carbachol are consistent with the hypothesis that carbachol antagonizes responses to alpha- and beta-receptor stimulation in left atria primarily by blocking increases in Ca2+ influx produced by these agonists.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sexual dimorphism in rat left atrial function and response to adrenergic stimulation

A number of investigations in humans and animals suggest that there may be intrinsic sex-associated differences in cardiac function. Using left atrial preparations from male and female rat hearts, we examined differences in myocardial function and response to adrenergic agonists. Contractile parameters were measured in isolated atria by conventional isometric methods in the absence or presence of isoproterenol or phenylephrine. Responsiveness to Ca²⁺ was measured in detergent-skinned atrial fibers and actomyosin ATPase activity was measured in isolated myofibrils. Tetanic contractions were generated by treating the atrium with ryanodine followed by high frequency stimulation. Developed force was greater and maximal rates of contraction and relaxation were more rapid in the female atrium. The relationship between Ca²⁺ concentration and force in both intact atria and detergent-skinned atrial fibers in females fell to the left of that for males. At low Ca²⁺ concentrations, skinned fibers from female atria generated more force and myofibrils from female atria had higher myosin ATPase activity than males. Tetanic contraction in the presence of high extracellular Ca²⁺ was greater in female atria. Male atrium had larger inotropic responses to isoproterenol and to phenylephrine, but drug-elicited cAMP and inositol phosphate production did not differ between sexes. The results demonstrate sex-related differences in atrial function that can be partially explained by greater myofibrillar Ca²⁺-sensitivity in females. A potential contribution of sarcolemmal Ca2+ influx is suggested by greater tetanic contraction in ryanodine-treated female atrium. The larger response of males to adrenergic stimulation does not appear to be explained by higher production of relevant second messengers. Future studies will investigate the role of sex hormones in these sexually dimorphic responses and may indicate a need for gender-specific therapeutic interventions for myocardial dysfunction.     

Adrenergic-cholinergic interactions in left atria: interaction of carbachol with alpha- and beta-adrenoceptor agonists

The purpose of the present investigation was to determine the nature of the functional interaction of muscarinic agonists with cAMP-generating and cAMP-independent agonists in left atria. Negative inotropic responses of rabbit isolated left atrial strips to the muscarinic agonist carbachol were measured in the absence and presence of equi-active inotropic doses of the beta-adrenoceptor stimulant isoproterenol (Iso), the mixed alpha- and beta-adrenoceptor stimulant phenylephrine (PE) plus 1 microM timolol to block the beta-receptor mediated component of its response, and elevated extracellular Ca2+. Carbachol produced dose-dependent negative inotropic responses in left atrial strips, which were much greater than control in the presence of either Iso, or PE plus timolol. However, carbachol responses were of a similar magnitude to the control in the presence of elevated extracellular Ca2+. In the presence of timolol, PE had no significant effect on cAMP levels in left atrial strips, and inotropic responses to carbachol alone and in combination with PE plus timolol were accompanied by significant increases in cGMP levels but no change in cAMP levels. Carbachol attenuated Iso-induced increases in cAMP levels, but decreases in left atrial tension were proportionally greater than the decreases in cAMP levels produced by carbachol in the presence of Iso. These results suggest that the antiadrenergic effects of muscarinic receptor stimulation may occur by a different mechanism in left atria than has been previously reported in ventricular muscle. While the nature of this mechanism is unknown, it may involve antagonism by muscarinic agents of both alpha- and beta-adrenoceptor mediated increases in Ca2+ influx.     

Oppositional effects of acetylcholine and isoproterenol on isometric tension and cyclic nucleotide concentrations in rabbit atria.

The effects of acetylcholine chloride and isoproterenol on myocardiial cyclic GMP, cyclic AMP and on isometric tension were studied in isolated electrically driven rabbit atria. Acetylcholine (0.5 muM) produced a significant decrease in isometric force that was associated with a significant elevation in atrial cyclic GMP. Cyclic AMP was significantly lowered at 15 seconds after the addition of acetylcholine, but was only slightly decreased at earlier time periods. Both the negative inotropic action and increase in cyclic GMP after addition of acetylcholine were blocked by atropine. Isoproterenol (0.1 muM) produced a significant increase in isometric tension that was associated with a significant elevation in atrial cyclic AMP levels, whereas cyclic GMP levels were not changed. These effects were blocked by practolol. The increases in atrial cyclic GMP and cyclic AMP following addition of acetylcholine and isoproterenol, respectively, preceded the changes in isometric tension in response to these agents. These data support the hypothesis that changes in intracellular levels of cyclic AMP and cyclic GMP may mediate the positive and negative inotropic effects of adrenergic and cholinergic agents.     

Desensitization of alpha-1 adrenergic receptor mediated smooth muscle contraction in aorta from endotoxic rats

Desensitization of vascular smooth muscles in endotoxemia was studied using the aorta from intraperitoneally endotoxin-injected rats. The KCl- and phenylephrine-induced contractions were significantly decreased in the endotoxic aorta compared to the control. In the endotoxic aorta the phenylephrine-induced contracture showed a gradual tension decrease after reaching a plateau and was attenuated by prior exposure to high concentration of phenylephrine, while KCl produced a sustained contraction and it was not affected by prior exposure to phenylephrine. The phenylephrine- and KCl-induced contractures of the control aorta showed stable plateaus and were not affected by prior exposure to phenylephrine. Neither diminished contractile force nor in vitro desensitization of phenylephrine contracture of isolated aorta was prevented by pretreatment of endotoxic rats with an alpha-adrenergic antagonist, phentolamine. These findings suggest that the contractile response to phenylephrine is easily desensitized in the endotoxic aorta compared to the control and neither this in vitro desensitization nor the diminution of contractile force is caused by in vivo exposure of aorta to a high concentration of catecholamines during endotoxemia.     

Cyclic AMP and the positive inotropic effect of norepinephrine and phenylephrine.

Time-response studies of the effects of norepinephrine and phenylephrine revealed that both agonists caused an increase in cyclic AMP levels before increases in contractile force in either the electrically stimulated left atria or spontaneously beating right atria of the rat. Norepinephrine caused a nearly sixfold increase in cyclic AMP, whereas phenylephrine produced only a 50% increase in the nucleotide. Pretreatment with reserpine did not affect the norepinephrine cyclic AMP response; however, the phenylephrine cyclic AMP response was abolished. Reserpine pretreatment did not significantly affect the contractile responses of either amine. In the presence of propranolol, norepinephrine was found to have the ability to produce an increace in contractile force in which cyclic AMP was apparently not involved. The time course of the contractile response induced by adrenergic amines was found to be remarkably influenced by the chronotropic response in spontaneously beating preparations while the cyclic AMP response was not greatly affected. This difference in the contractile response may be due to the ability of the chronotropic response to influence the flux of calcium through the cell membrane.     

Species comparison of adenosine A1 receptors in isolated mammalian atrial and ventricular myocardium

Various species have been used as models to study the effects of adenosine (ADO) on atrial and ventricular myocardium, but few direct tissue comparisons between species have been made. This study further characterizes adenosine A(1) receptor binding, adenylate cyclase activity and direct and indirect A(1) receptor-mediated functional activity in atrial and ventricular tissue from Sprague-Dawley rats and Hartley guinea pigs. Rat right atria (RA) were found to be significantly more sensitive to cyclopentyladenosine (CPA), while guinea pig left atria (LA) were more sensitive to CPA. After the addition of isoproterenol (ISO), the reduction of CPA response in rat RA was significantly greater than in guinea pig; however, after ISO treatment, the guinea pig LA was more sensitive to CPA than the rat. Adenylate cyclase inhibition by CPA was significantly greater in atria and ventricles obtained from guinea pig than rat. In competition binding experiments, guinea pig RA had significantly more high affinity sites than rat, but the K(i)s were not significantly different. There were no significant differences between guinea pig LA and rat LA. Guinea pig ventricular tissue had fewer high affinity sites than rat without any differences in their K(i) values. In antagonist saturation experiments, the density and affinity of A(1) receptors in guinea pig cardiac membranes were significantly greater than in rat. Our results indicate definite species differences as well as tissue differences between rat and guinea pig. These differences must be considered when interpreting studies using rat and guinea pig tissue as models for cardiac function.     

Different response of ANP secretion to adrenoceptor stimulation in renal hypertensive rat atria

Sympathetic nervous system and atrial natriuretic peptide (ANP) system play fundamental roles in the regulation of cardiovascular functions. Overactivity of sympathetic nervous system can lead into cardiovascular diseases such as heart failure and hypertension. The present study aimed to define which adrenergic receptors (ARs) affect atrial contractility and ANP release and to determine their modification in renal hypertensive rat atria. An alpha(1)-AR agonist, cirazoline increased ANP release with positive inotropism. These alpha(1)-AR agonist-mediated responses were attenuated by the alpha(1A)-AR antagonist, but not by the alpha(1B)- or alpha(1D)-AR antagonist. An alpha(2)-AR agonist, guanabenz and clonidine increased ANP release with negative inotropism and decreased cAMP level. The order of potency for the increased ANP release was cirazoline>phenylephrine=guanabenz>clonidine. In contrast, a beta-AR agonist, isoproterenol decreased ANP release with positive inotropism and these responses were blocked by the beta(1)-AR antagonist but not by the beta(2)-AR antagonist. The increased cAMP level by isoproterenol was suppressed by pretreatment with both beta(1)- and beta(2)-AR antagonists. In renal hypertensive rat atria, the effects of isoproterenol on atrial contractility, ANP release, and cAMP level were attenuated whereas the effect of cirazoline on ANP release was unaltered. Atrial beta(1)-AR mRNA level but not alpha(1A)-AR mRNA level was decreased in renal hypertensive rats. These findings suggest that alpha(1A)- and beta(1)-AR oppositely regulate atrial ANP release and that atrial beta(1)-AR expression/function is impaired in renal hypertensive rats.     

On the stimulation of respiration by alpha-adrenergic agonists in perfused rat liver

Interactions between phenylephrine-induced oxygen consumption, lactate and pyruvate output, and urea and glucose production were examined in perfused livers from fed or 48-h-fasted rats. Within 2 min of phenylephrine infusion, oxygen consumption in perfused livers was increased by approximately 40%. Increases in oxygen consumption induced by phenylephrine were essentially abolished in the presence of carboxyatractyloside, whereas those induced by dinitrophenol were still evident. Phenylephrine-induced increases in oxygen consumption were accompanied by enhanced rates of gluconeogenesis and ureogenesis in livers from fed or 48-h-fasted animals. These data indicate that phenylephrine-induced increases in respiration in perfused rat liver may result from an enhanced rate of mitochondrial oxidative phosphorylation in response to an increased cellular energy requirement.     

Alterations in alpha 1-adrenoceptor stimulation of isolated atria from experimental diabetic rats

This purpose of this investigation was to determine the influence of experimental diabetes (3 months) on the responsiveness of rat isolated atria to alpha 1-adrenoceptor stimulation by phenylephrine. Diabetes was chemically induced with streptozotocin (65 mg/kg i.v.) in 42- to 43-day-old, nonfasted male Sprague-Dawley derived rats. Chronotropic (right atria) and inotropic (left atria) indices were recorded in response to alpha 1-adrenoceptor stimulation by phenylephrine. These experiments were performed in the presence of beta-adrenoceptor antagonism (timolol). Isolated right atria from diabetic rats demonstrated a greater increase in heart rate in response to phenylephrine than did corresponding control atria. Left atria were supersensitive (decrease in EC50 values) and hyperresponsive to alpha 1-adrenoceptor stimulation by phenylephrine when compared with stimulation of control left atria. Diabetic left atria in response to phenylephrine were observed to exchange more radioactive calcium (45Ca2+) than control left atria, whereas both diabetic and control left atria exchanged the same amount of 45Ca2+ during basal contractile conditions. Phenylephrine had no effect on 45Ca2+ efflux from either diabetic or control atria. These results indicate that 3 months of uncontrolled experimental diabetes in the rat produces an enhancement of alpha 1-adrenoceptor activation of isolated atria, and that there is an alteration in Ca2+ mobilization which may contribute to the enhanced receptor activation.     

Adrenergic reactivity of the myocardium in hypertension

Adrenoceptor-mediated inotropic and chronotropic responses have been studied in isolated atria from a younger and an older group of spontaneously hypertensive (SHR) and age-matched normotensive rats (NR). The isoproterenol/phenylephrine potency ratios were significantly lower in the older SHR than in age-matched NR. Exposure of left atria to cocaine, iproniazid and tropolone to inhibit major pathways of agonist inactivation significantly enhanced the potency of both agonists in NR but did not influence agonist potencies in SHR and the agonist potency ratios remained different in the two groups. Inotropic responses to phenylephrine were blocked by metoprolol less effectively and by phentolamine more effectively in older SHR than in NR. Atrial sensitivity to isoproterenol was significantly higher in the younger than in the older SHR. Chronic treatment of SHR with propranolol, 5–20 mg/kg/day i.p. from age 4 to 14 weeks and stopped 2 days before the experiment, limited the increase in blood pressure and increased the potency of isoproterenol and decreased the potency of phenylephrine to or beyond levels in NR. The effectiveness of adrenoceptor antagonists in SHR did not significantly change with age or after propranolol treatment. The results were interpreted to indicate that 1) mechanisms of agonist inactivation are impaired or non-functional in the SHR myocardium; 2) there is a shift in the balance of cardiac inotropic adrenoceptors from β toward α between normotensive and hypertensive rats, and 3) β-adrenoceptors are subsensitive in adult SHR, but become supersensitive to isoproterenol after chronic treatment with propranolol.     

Biochemically stimulated release of atrial natriuretic factor from heart-lung preparation of Dahl rats

We investigated the effect of sodium chloride and adrenergic agents on the release of atrial natriuretic factor (ANF) using working heart-lung preparations from Dahl salt-hypertension sensitive (S) and Dahl salt-hypertension resistant (R) rats. High concentrations of NaCl moderately increased ANF release, but this was attributed to small increases in left atrial pressure rather than to a direct effect of NaCl on ANF release; S and R rats responded similarly. Neither isoproterenol (beta 1 + beta 2 agonist) nor clonidine (alpha 2 agonist) had any effect on ANF release in the heart-lung preparation. In contrast, phenylephrine (alpha 1 agonist) stimulated ANF release. This could not be accounted for by change in atrial pressure and appeared to be a direct effect. S and R rats both released ANF in response to phenylephrine, but there was a modest tendency for hypertensive S rats to release more ANF than normotensive R rats, which is consistent with previous data on mechanically induced (atrial stretch) ANF release in these strains.     

Accentuation of ursolic acid on muscarinic receptor-induced ANP secretion in beating rabbit atria

Aims

Ursolic acid has recently been reported to increase both atrial natriuretic peptide (ANP) secretion and mechanical dynamics in rabbit atria.

Main methods

The present study was designed to clarify the regulatory effects of ursolic acid on the β-adrenergic or muscarinic receptor-mediated changes in ANP secretory and contractile function allowing measurement of atrial dynamics such as pulse pressure, stroke volume, and cAMP efflux in isolated perfused beating rabbit atria.

Key findings

Pretreatment with ursolic acid significantly attenuated the isoproterenol (β-adrenergic agonist)-induced decrease in ANP secretion and increases in cAMP levels and atrial dynamics. Interestingly, ursolic acid concentration-dependently accentuated the acetylcholine-induced increase in ANP secretion and decrease in pulse pressure in the presence of isoproterenol (p < 0.001). These findings indicate that acetylcholine-induced increase in ANP secretion is potentiated by ursolic acid; furthermore, acetylcholine-induced decrease in atrial dynamics is also potentiated by ursolic acid, suggesting that ursolic acid regulates muscarinic receptor-mediated secretory and contractile responses in perfused beating rabbit atria.

Significance

This implicates for the beneficial effects of ursolic acid in the regulation of cardiovascular and body fluid homeostasis.     

Kinetic characteristics of hamster (Mesocricetus auratus) brown fat (Na+/K+)-ATPase: effects of catecholamines

1. The (Na+/K+)-ATPase activity of brown fat membranes is increased by norepinephrine, the physiological mediator of thermogenesis in this tissue. 2. This increased ATPase activity was inhibited approximately 50% by either propranolol (a beta-adrenergic blocker) or phentolamine (an alpha-blocker). 3. The alpha-agonist, phenylephrine and the beta-agonist, isoproterenol, also stimulated the ATPase activity. 4. That these latter effects were receptor-specific is supported by the finding that: (a) l(-)isoproterenol stimulation was inhibited by propranolol but not by phentolamine; (b) d(+)isoproterenol had no stimulatory effect on the ATPase activity; and (c) the l(-)phenylephrine-induced increase was inhibited by phentolamine but not by propranolol. 5. (-)norepinephrine, l(-)isoproterenol and l(-)phenylephrine all decreased the apparent Km for K+ of the (Na+/K+)-ATPase but did not alter the apparent Km for ATP or the Vmax of the reaction.     

The inotropic effect of endothelin-1 on rat atria involves hydrolysis of phosphatidylinositol

Endothelin-1 induces a positive inotropic response in isolated left atria of the rat with an IC50 value of 20 nM. The contractile effect of endothelin is larger than that of other inotropic hormones such as phenylephrine and epinephrine and smaller than that of Bay K8644. In the spontaneously active right atria, endothelin induces a positive inotropic effect with no chronotropic effect. Endothelin does not modify intracellular levels of cAMP under basal conditions or after stimulation with isoproterenol but stimulates the formation of inositol phosphates. Mobilization of inositol phospholipids is observed in the same range of concentrations as for the contractile action of endothelin. The contractile action of endothelin is not mediated by protein kinase C. It is antagonized by blockers of L-type Ca2+ channels, low external Ca2+ concentrations and drugs such as caffeine and ryanodine that interfere with Ca2+ release by the sarcoplasmic reticulum.     

Effects of ischaemia,reperfusion and α1 receptor stimulation on the inositoltrisphosphate receptor population in rat heart atria and ventricles

Binding sites specific for inositol 1,4,5-trisphosphate (InsP₃) have been demonstrated in sarcoplasmic reticulum vesicles isolated from heart muscle. Scatchard analysis of a binding isotherm indicated a high as well as a low affinity binding site [1]. In this study a comparison was made between InsP₃ binding to crude microsomal membranes prepared from rat heart atria and ventricles respectively. Results obtained showed a four-fold higher incidence of binding to atrial membranes. Furthermore, the receptor populations of the atria and ventricles behaved differently during conditions causing fluctuations in tissue InsP₃ levels, viz. ischaemia, reperfusion and ₁-adrenergic stimulation. Reperfusion, as well as phenylephrine stimulation, caused an increase in InsP₃ levels associated with down-regulation of the ventricular InsP₃ receptor population while binding to atrial binding sites was elevated. In the ventricular population this down-regulation was the result of a reduction in B_max alone with no changes in the Kd values of the high- or the low-affinity binding sites. The reason(s) for the differential response of the atrial and ventricular InsP₃ receptor populations to changes in InsP₃ levels, remains to be established.     

Effects of the adrenergic nervous system on training-induced cardiac enlargement, and on the intrinsic rate and phenylephrine sensitivity of isolated rat atria

Atria isolated from rats after 6 to 7 weeks running training or swim training in water at 30 degrees C beat at a slower rate than did the atria from sedentary control animals. If the rats received noradrenaline injections with each running session their atrial rate was even lower, while propranolol injections did not lead to lower intrinsic atrial rate. Repeated noradrenaline or propranolol injections alone or swim training in warm water (38 degrees C) did not result in altered atrial rate. A plot of the intrinsic atrial rate against heart weight yielded a significant (r = -0.803) negative relationship (y = 311 - 0.91 x). Swim training in cold water, or chronic noradrenaline injections led to a lessened sensitivity of isolated atria to phenylephrine while chronic beta blockade tended to increase the sensitivity. The results suggest that an intense, although transient, cardiac stimulation, typical of the combined action of running training and noradrenaline injections, results in a lower intrinsic atrial rate and greater cardiac enlargement, while a more sustained type of cardiac stimulation, as produced typically by repeated injections of noradrenaline, leads to less sensitivity to phenylephrine.     

Hormonal stimulation of cyclic AMP accumulation and glycogen phosphorylase activity in calcium-depleted hepatocytes from euthyroid and hypothyroid rats.

Activation of glycogen phosphorylase by hormones was examined in hepatocytes isolated from euthyroid and hypothyroid female rats and incubated by Ca2+-free buffer containing 1 mM-EGTA. Basal glycogen phosphorylase activity was decreased in Ca2+-free buffer. However, the activation of hepatocyte glycogen phosphorylase, in the absence of extracellular Ca2+, in response to adrenaline, glucagon or phenylephrine was slightly lower, whereas that by vasopressin was abolished. The activation of glycogen phosphorylase by phenylephrine, adrenaline or isoproterenol (isoprenaline) in hepatocytes from euthyroid rats incubated in the absence of Ca2+ was not accompanied by any detectable increase in total cyclic AMP. The log-dose/response curves for activation of phosphorylase by phenylephrine or low concentrations of adrenaline were the same in hepatocytes from hypothyroid as compared wit euthyroid rats, whereas the response to isoproterenol was greater in hepatocytes from hypothyroid rats. However, the increases in total cyclic AMP accumulation caused by adrenaline or isoproterenol were greater in hepatocytes from hypothyroid rats than in hepatocytes from euthyroid rats. The increases in cyclic AMP accumulation caused by adrenaline or isoproterenol in Ca2+-depleted hepatocytes from hypothyroid rats were blocked by propranolol, a beta-adrenergic antagonist. In contrast, propranolol was only partially effective asan inhibitor of the activation of glycogen phosphorylase by phenylephrine or adrenaline in hepatocytes from hypothyroid rats and ineffective on phosphorylase activation in cells from euthyroid rats. These data indicate that the alpha-adrenergic activation of glycogen phosphorylase is not affected by the absence of extracellular Ca2+, and the extent to which total cyclic AMP was increased by adrenergic amines did not correlate with glycogen phosphorylase activation.     

Right atrial predominance of atrial natriuretic peptide secretion in isolated perfused rat atria.

In order to investigate the regulatory mechanism for the atrial release of atrial natriuretic peptide (ANP), a perfused rabbit atrial model was devised. In the present experiments, the effect of a reduction in atrial distension on the immunoreactive ANP (irANP) secretion was investigated and compared in the perfused right and left atria of rats. Elevations in right and left atrial pressure resulted in proportional increases in the volume of atrial distension-reduction which was larger in the right than in the left atria. The basal rate of irANP secretion was higher in the right than in the left atria. Increases in the volume of atrial distension-reduction resulted in proportional increases in irANP secretion in both atria. Increment in irANP secretion in response to a reduction in atrial distension was significantly higher in the right than in the left atria. Higher rate of irANP secretion in response to unit volume change was observed in the right atria. Increases in the volume of atrial distension-reduction resulted in accentuated irANP responses in the right atrium. IrANP content was significantly higher in the right than in the left atria. The results suggest that the right atrium is a predominant site in ANP secretion in rats.