Ventricular Myocardium Of Dogs Research Articles

Effects of bimoclomol, the novel heat shock protein coinducer, in dog ventricular myocardium

The effects of the novel HSP-coinducer bimoclomol was studied on action potentials, ionic currents and [Ca 2+] i transients in isolated canine ventricular myocytes using conventional microelectrode techniques and whole cell voltage clamp combined with fluorescent [Ca 2+] i measurements. Contractility was studied in right ventricular trabeculae. All preparations were paced with a frequency of 0.2 Hz. Bimoclomol (100 μM) shortened action potential duration measured at 50% repolarization, but lengthened action potentials at the 90% repolarization level, decreased action potential amplitude and maximum depolarization velocity in a reversible manner. In voltage clamped myocytes, the drug activated a steady-state outward current at positive membrane potentials leaving the peak inward current unaffected. [Ca 2+] i transients, measured under voltage clamp control, were increased in amplitude and had accelerated decay kinetics in the presence of the compound, in addition to reduction of diastolic [Ca 2+] i. Bimoclomol significantly decreased the force of contraction in right ventricular trabeculae. Comparison of present data to previous results indicate that the cardiac effects of bimoclomol strongly depend on actual experimental conditions. The reduced contractility in spite of the increased amplitude of [Ca 2+] i transients suggests that 100 μM bimoclomol may decrease calcium sensitivity of the contractile apparatus.

Biphasic inotropic response to endothelin-1 in the presence of various concentrations of norepinephrine in dog ventricular myocardium.

The present study was undertaken to investigate the interaction between endothelin-1 (ET-1) and norepinephrine (NE) on contractile regulation in dog ventricular myocardium. ET-1 alone did not elicit any inotropic response in isolated dog ventricular trabeculae (37 degrees C, 0.5 Hz). In the presence of NE at a high concentration (10(-7) M), ET-1 (10(-8) M) elicited a long-lasting negative inotropic effect, while in the presence of NE at a moderate concentration (3 x 10(-8) M) it produced a biphasic inotropic effect: a sustained positive inotropic effect subsequent to a short-lasting negative inotropic effect. In the presence of a lower concentration (10(-9) M) that affected scarcely the basal force of contraction, ET-1 produced a pronounced positive inotropic effect in association with negative lusitropic and negative clinotropic effects in a concentration-dependent manner subsequent to a small transient negative inotropic effect. The presented results indicate that not only the extent, but also the quality of the inotropic response to ET-1 is determined by the level of NE in the biophase. The crosstalk of ET-1 with NE may play a crucial role in pathophysiological regulation of cardiac contractility in intact dog ventricular myocardium.

Preface

We observed that heterozygous knockout (+/-, KO) of either endothelin-A- (ET(A)) or -B- (ET(B)) receptors significantly reduced the pressor responses to systemically administered endothelin-1 (ET-1) in ET(A) or ET(B) (+/-) KO mice when compared to wild-type (WT) mice (data not shown). Also, we observed that basal mean arterial pressure (MAP) is significantly higher in ET(B) (+/-) (92.7 +/- 1.2 mmHg) (n = 53, p < 0.05) but not ET(A) (+/-) KO mice (70.6 +/- 1.8 mmHg) (n = 23) when compared to their anaesthetized WT littermates (70.1 +/- 0.7 mmHg) (n = 118). A 90 min treatment with either BQ-123 (10 mg/kg), an ET(A)-selective antagonist, or BQ-928 (10 mg/kg), a mixed ET(A)/ET(B) antagonist, administered intraperitoneally, significantly reduced basal MAP of ET(B) (+/-) KO mice almost to the level of their WT treated counterparts (94.9 +/- 4.9 mmHg) (n = 6) vs (+ BQ-123: 59.7 +/- 0.3 mmHg, n = 8); (+ BQ-928: 72.4 +/- 2.6 mmHg, n = 5). It is worthy of note that BQ-123 significantly reduced basal MAP in WT mice but to a lesser extent than in ET(B) (+/-) KO mice (69.6 +/- 2.3 mmHg, n = 8) vs (+ BQ-123: 57.3 +/- 1.4 mmHg, n = 8). In contrast, the ET(B)-selective antagonist, BQ-788 (10 mg/kg i.p.), had no significant effect on MAP even after 90 min of treatment (ET(B) (+/-) KO: (92.3 +/- 2.3 mmHg, n = 6) vs (+ BQ-788: 89.7 +/- 3.1 mmHg, n = 6); WT: (70.5 +/- 3.7 mmHg, n = 7) vs (+ BQ-788: 71.2 +/- 2.0 mmHg, n = 6). Therefore heterozygous KO of either ET(A)- or ET(B)-receptors significantly alters the phenotypic pressor properties of ET-1. We also suggest that there is less ET clearance in ET(B) (+/-) KO mice than in WT mice, which can explain the ET(A)-dependent hypertensive state of the former strain.

Laser catheter coagulation of normal and scarred ventricular myocardium in dogs.

Larger lesions would increase success rates of catheter ablation of ventricular arrhythmias. Therefore, improved radio frequency current application techniques, but also alternative energy sources, are being investigated. The purpose of this study was to determine morphology and dimensions of ventricular lesions induced by transcatheter application of laser energy. A total of 244 lesions were produced by Nd:YAG laser pulses, 1,064 nm, 10-30 W, 15-60 s, percutaneously (endocardial approach, n = 124) and under visual control (epicardial approach, n = 120) in the left ventricular walls of 24 anesthetized dogs. Dimensions of lesions increased with the amount of energy applied. Maximal values were obtained at 20 W, 60 s: depth = 12.6 +/- 1.1 mm (transmural); width = 15.0 +/- 2.8 mm; volume = 1,582 +/- 777 mm3. Volumes of lesions did not change significantly when induced through previously scarred myocardium. Histologically, lesions were clear-cut, without crater or thrombus formation. Procedures and follow-up periods of up to 22 months were without complications. Nd:YAG laser pulses at 10-20 W and 15-60 s produce homogeneous myocardial lesions of coagulation necrosis of reproducible sizes, in a controllable manner, without unwanted effects on the ventricular walls, in normal and through scarred myocardium of dogs. The laser method is a promising alternative for ablation of ventricular arrhythmias including candidates with ischemic heart disease.

SR Ca(2+)-ATPase activity and expression in ventricular myocardium of dogs with heart failure.

The purpose of this study was to examine the activity and expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase in left ventricular (LV) myocardium of dogs with chronic heart failure (HF). LV and right ventricular (RV) tissue specimens were obtained from six normal (NL) control dogs and six dogs with chronic HF (LV ejection fraction, 23 +/- 2%) produced by multiple sequential intracoronary microembolizations. Thapsigargin-sensitive Ca(2+)-ATPase activity was measured in isolated SR membrane fractions prepared from LV and RV myocardium. Ca(2+)-ATPase expression, using a specific dog myocardium monoclonal antibody, was measured in sodium dodecyl sulfate (SDS) extract prepared from LV and RV myocardium. Ca(2+)-ATPase activity in both ventricles of NL or HF dogs increased with increasing Ca2+ concentration and reached a plateau at 3 microM Ca2+. The maximal velocity (Vmax, mumol Pi released.min-1.mg-1) of Ca(2+)-ATPase activity was significantly lower in LV of HF dogs compared with NL (0.15 +/- 0.01 vs. 0.23 +/- 0.01, P < 0.05), whereas the affinity of the Ca2+ pump for Ca2+ was unchanged. LV tissue levels of Ca(2+)-ATPase (densitometric units/5 micrograms noncollagen protein) were also significantly lower in LV myocardium of HF dogs compared with NL (3.52 +/- 0.43 vs. 5.53 +/- 0.47, P < 0.05). No significant differences in Ca(2+)-ATPase activity or expression were observed in RV myocardium of HF dogs compared with NL. We conclude that SR Ca(2+)-ATPase activity and protein levels are reduced in LV myocardium of dogs with chronic HF. This abnormality of the SR Ca2+ pump of the failed LV can result in impaired Ca2+ uptake and ultimately to Ca2+ overload and global LV dysfunction.

P-474 - Pertussis toxin sensitive G protein mediates the inhibitory action of endothelin-1 on the positive inotropic response to β stimulation in dog ventricular myocardium

P-474 - Pertussis toxin sensitive G protein mediates the inhibitory action of endothelin-1 on the positive inotropic response to β stimulation in dog ventricular myocardium

Enalapril but not metoprolol improves capillary density and oxygen diffusion distance in left ventricular myocardium of dogs with moderate heart failure

Enalapril but not metoprolol improves capillary density and oxygen diffusion distance in left ventricular myocardium of dogs with moderate heart failure

Preliminary results using ultrasound energy for ablation of the ventricular myocardium in dogs.

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The Effects of Theophylline on Aequorin Light Transients and Force in the Isolated Dog Right Ventricular Myocardium

Experiments were carried our to investigate the changes in intracellular Ca 2+ transients associated with biphasic contractions that were elicited during interaction of theophylline with isoproterenol in the dog ventricular myocardium. For this purpose, effects of theophylline and isoproterenol on aequorin light transients and isometric contractions were assessed in the isolated canine ventricular trabeculae, superficial cells of which had been microinjected with the Ca 2+ sensitive bioluminescent protein aequorin. The positive inotropic effect of theophylline (0.1-0.3 mM) was consistently associated with an increase in the amplitude of aequorin light transients. Theophylline at concentrations of 0.6 mM and higher decreased the amplitude of aequorin light transients, but the force of contraction increased further in association with a prominent prolongation of time to peak force. Theophylline (0.3 mM) enhanced the forskolin-induced increase in aequorin light transients and force. Theophylline (2 mM) inhibited the isoproterenol-induced increase in aequorin light transients associated with early phase of contraction in a reversible manner. A late phase of aequorin light transients was induced in association with late phase of contraction in the presence of both isoproterenol and theophylline. Thus, both the early and late phase of contraction were accompanied by corresponding phases of aequirin light transients. The relation between the amplitude of force and Ca 2+ transients was markedly different and the late phase of contraction was associated with much lower aequorin light transients. The late phase of aequorin light transients induced by theophylline at a high concentration (10 mM) was enhance by isoproterenol. These results indicate that theophylline (0.1-0.3 mM) increases the amplitude of Ca 2+ transients through an accumulation of cyclic AMP by inhibition of the cyclic AMP phosphodiesterase activity. In concentrations of 0.6 mM and higher theophylline decreases the amplitude of the early phase aequorin light transients probably by inhibition of release of Ca 2+ from the sarcoplasmic reticulum and induces simultaneously the late phase of contraction that may be associated with an increase in responsiveness to Ca 2+ of myofibrils.

O-136 - Subcellular mechanism of the positive inotropic effect of a new cardiotonic agent Org 9731 on the dog ventricular myocardium.

O-136 - Subcellular mechanism of the positive inotropic effect of a new cardiotonic agent Org 9731 on the dog ventricular myocardium.

Phasic characteristics of arterial inflow and venous outflow of right ventricular myocardium in dogs.

To clarify the characteristics and causes of phasic blood flow in coronary circulation of the right ventricle we measured blood velocities in peripheral portions of the right coronary artery and vein in dogs under three conditions: control, transient pulmonary stenosis, and isoproterenol administration. An optical fiber sensor of a laser Doppler velocimeter was fixed onto the vessels (150-500 microns OD) with cyanoacrylate. The phasic pattern of distal arterial velocity was compared with the proximal velocity in the right coronary artery measured with an ultrasound pulsed Doppler velocimeter. Systolic-to-total velocity area ratio in the small epicardial artery [0.38 +/- 0.03 (SE)] was found to be smaller than in the large epicardial artery (0.51 +/- 0.02, P less than 0.01), indicating a capacitive filling of the epicardial artery during systole. The velocity waveform in small right coronary veins was predominantly systolic; i.e., it increased with a rise of right ventricular pressure and decreased with right ventricular relaxation. Comparison of the waveforms during isoproterenol infusion and pulmonary stenosis indicates that contraction of the ventricle is more important than right ventricular systolic pressure in retarding arterial inflow and accelerating venous outflow.

A unique positive inotropic agent Org 30029 acts by increase in calcium sensitivity of contractile proteins in the intact dog ventricular myocardium

A unique positive inotropic agent Org 30029 acts by increase in calcium sensitivity of contractile proteins in the intact dog ventricular myocardium

Subcellular mechanism of the positive inotropic effect of a new quinolinone derivative OPC-8490 on the dog ventricular myocardium.

OPC-8490 [3,4-dihydro-6-[4-(4-oxo-4-phenylbutyl)-1- piperazinylcarbonyl]-2(1H)-quinolinone citrate] elicited a positive inotropic effect in a concentration-dependent manner on the isolated dog ventricular trabeculae electrically driven at 0.5 Hz in Krebs-Henseleit solution bubbled with 95% O2-5% CO2 at 37 degrees C. The beta-adrenoceptor antagonist, bupranolol (3 x 10(-7) mol/l), did not influence the effect of OPC-8490. The maximal effect of OPC-8490 was 0.19 compared with isoproterenol (1.0). The time course of the increase in contractile force coincided with that of the concomitant cyclic AMP accumulation induced by OPC-8490. The concentration-response curve for the OPC-8490-induced increase in contractile force was superimposable on that of the elevation of cyclic AMP levels. OPC-8490 (10(-5) mol/l) shifted the concentration-response curve for isoproterenol to the left and upward. These results imply that the accumulation of cyclic AMP induced by OPC-8490 through an inhibition of peak III PDE may be responsible for its positive inotropic effect. However, the OPC-8490-induced increase in the contractile force was not abolished by carbachol (3 x 10(-6) mol/l) when the cyclic AMP accumulation caused by the compound was completely inhibited by carbachol. In addition, OPC-8490 did cause a change in the time course of isometric contractions characteristic of cyclic AMP accumulation. These findings indicate that both the cyclic AMP-dependent (peak III PDE inhibition) and the cyclic AMP-independent mechanisms (prolongation of action potential duration by inhibition of K+ conductance) may be involved in the positive inotropic effect of OPC-8490 on the dog ventricular muscle.

Characterization of positive inotropic effect of endothelin on mammalian ventricular myocardium.

Endothelin-1 elicited a positive inotropic effect (PIE) on isolated rabbit, guinea pig, and rat but not on dog ventricular myocardium. Specific high-affinity binding of 125I-labeled endothelin-1 was detected in the ventricular membrane fraction of these species. Maximal binding capacity was the highest in the rabbit, lowest in the dog, and in between in the guinea pig and rat; this rank order corresponds roughly to the effectiveness of endothelin-1 in producing a PIE. There was no difference in the potency or efficacy for the PIE of the endothelin isoforms endothelin-1, -2, and -3 in the rabbit papillary muscle. A tumor-promoting phorbol ester, phorbol 12,13-dibutyrate, inhibited selectively the PIE and the accumulation of [3H]inositol monophosphate induced by endothelin-1 as well as those of myocardial alpha 1-adrenoceptor stimulation in a concentration that did not (10(-8) M) or only slightly (10(-7) M) reduced the PIE of BAY K 8644. Phorbol 12,13-dibutyrate did not affect the specific binding of 125I-labeled endothelin-1 in the ventricular membrane fraction of the rabbit. The present findings indicate that the characteristics of the endothelin-induced PIE in mammalian ventricular myocardium are similar to those of myocardial alpha 1-adrenoceptor activation that may involve phosphoinositide hydrolysis. The receptor density and the PIE of endothelin on mammalian cardiac muscle show a wide range of variation among species.

Pharmacological characteristics of adenosine-induced inhibition of dog ventricular contractility: dependence on the pre-existing level of ?-adrenoceptor activation

Experiments were carried out to characterize the adenosine-induced negative inotropic effect in relation to the extent of beta-adrenoceptor activation in the isolated dog left ventricular myocardium. Adenosine and R-N6-phenylisopropyladenosine inhibited the positive inotropic effect of isoprenaline (10(-7) mol/l and lower) about 20% of its maximal response, which was antagonized by an A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine in a concentration-dependent manner. The negative inotropic effect of adenosine disappeared and that of R-N6-phenylisopropyl-adenosine decreased when the isoprenaline concentration was elevated to the level higher than 10(-7) mol/l. Adenosine deaminase (1.5 U/ml) that abolished the negative inotropic effect of adenosine enhanced the effect of R-N6-phenylisopropyladenosine, indicating that endogenous adenosine released by high isoprenaline concentration (10(-6) mol/l) modulates the interaction. The maximal response to adenosine and R-N6-phenylisopropyladenosine determined in the presence of 10(-7) mol/l isoprenaline was 50% of that of carbachol which elicited the maximal inhibition even in the presence of 10(-6) mol/l isoprenaline. The negative inotropic effects of R-N6-phenylisopropyladenosine and carbachol were additive to the maximal response equivalent to that of carbachol. The difference in the efficiency between the adenosine and muscarinic receptor agonists may be partly ascribed to the difference in densities of the respective receptors in the dog ventricular myocardium. The negative inotropic effect of R-N6-phenylisopropyladenosine in the presence of isoprenaline was associated with decrease in cyclic AMP levels elevated previously by isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial alpha 1-adrenoceptors mediate positive inotropic effect and changes in phosphatidylinositol metabolism. Species differences in receptor distribution and the intracellular coupling process in mammalian ventricular myocardium.

Species-dependent variations of myocardial alpha 1-adrenoceptor-mediated positive inotropic effects of epinephrine were assessed in relation to characteristics of alpha 1-receptor bindings and acceleration of phosphatidylinositol metabolism in the isolated rat, rabbit, and dog ventricular myocardium. Epinephrine in the presence of the beta-adrenoceptor antagonist bupranolol (10(-6) M) elicited a positive inotropic effect through activation of alpha 1-adrenoceptors in rat and rabbit, whereas in dog ventricular myocardium, bupranolol abolished the positive inotropic effect of epinephrine. [3H]Prazosin bound to membrane fractions derived from rat, rabbit, and dog ventricular muscle with high affinities in a saturable and reversible manner. In dog, Bmax and Kd values of alpha 1-adrenoceptor binding sites were identical to those in rabbit ventricular muscle. The Bmax value of alpha 1-adrenoceptors in rat ventricle was the highest, amounting to two to four times those in rabbit and dog. Epinephrine displacement curves for the specific binding of [3H]prazosin in the membrane fraction of these species showed high and low affinity sites with slope factors significantly less than unity, which were shifted to single low affinity sites with slope factors close to unity by addition of 5'-guanylylimidodiphosphate. Accumulation of [3H]inositol 1-phosphate [( 3H]IP1) in ventricular slices prelabeled with [3H]myo-inositol was increased by epinephrine in a time- and concentration-dependent manner in rat ventricular slices. [3H]IP1 accumulation likewise was facilitated by alpha 1-adrenoceptor stimulation in rabbit ventricular slices, whereas the extent of [3H]IP1 accumulation was much less than that in rat. In dog ventricular slices, [3H]IP1 was not accumulated by epinephrine. In rabbit papillary muscle, the time course of increase in contractile force induced by alpha-adrenoceptors coincided with the prolongation of the action potential duration with a similar time course, which is in strong contrast to previous findings in rat that the contractile response was dissociated from the electrophysiological response to alpha-adrenoceptor stimulation. The present results indicate that a wide range of variation of alpha 1-adrenoceptor-mediated regulation of myocardial contractility may be ascribed to different contributions of facilitatory as well as inhibitory regulatory processes that lead to intracellular Ca2+ mobilization subsequent to myocardial alpha 1-adrenoceptor activation among mammalian species.

Mr40,000 and Mr 39,000 Pertussis Toxin Substrates Are Increased in Surgically Denervated Dog Ventricular Myocardium

To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function.

Measurement of Regional

We measured blood flow within each of eight segments of the left ventricular myocardium in dogs by an Ultrafast CT scanner. The results were compared with flow determined by radiolabeled microspheres. Computed tomography (CT) flow was measured by an intravenous injection of nonionic contrast agent done simultaneously with the left atrial injection of microspheres. We calculated flow from the CT data by obtaining CT number versus time curves for regions of interest in the myocardium and by using a formula that related flow to both the time and value of the peak enhancement. Measurements were obtained in five dogs at rest and during hyperperfusion induced by chromonar. Based on 169 regional measurements, the Ultrafast CT and microsphere-determined flows correlated moderately (r = 0.68) over a range of 0.4 to 8 mL/min/g. However, when the data were divided into resting and hyperperfusion (ie, 20 to 30 minutes after the injection of the chromonar) states, a significant (P less than .001) increase in regional flow was determined from the CT measurements. The conclusion was that Ultrafast CT can distinguish between low and high myocardial flow states in dogs and has considerable potential for evaluating coronary flow reserve.

Transient outward current prominent in canine ventricular epicardium but not endocardium.

Previous studies have denied the presence of a transient outward current (Ito) in ventricular myocardium of dog, sheep, and calf. Using conventional microelectrode techniques, we provide evidence for a significant contribution of Ito to epicardial, but not endocardial, activity of canine ventricular myocardium. The epicardial action potential when compared with that of endocardium shows a smaller phase 0 amplitude, a much more prominent phase 1, and a phase 2 amplitude that is greater than that of phase 0. Epicardial action potentials, unlike those of endocardium, display a "spike and dome" morphology that becomes progressively more accentuated at slower stimulation rates. Using the restitution of phase 1 amplitude as a marker for the process responsible for the spike and dome phenomenon, we were able to delineate two exponential components: 1) a slow component that recovers with a time constant of 350-570 msec and 2) a fast component with a time constant of 41-85 msec. The slow component was largely abolished by 1-5 mM 4-aminopyridine, an Ito blocker. The fast component was diminished by 4-aminopyridine, but it was also inhibited by ryanodine and by Sr2+ replacement of Ca2+, which are interventions known to inhibit the Ca2+-activated component of Ito. Following 4-aminopyridine and Sr2+ or ryanodine treatment, the epicardial responses more closely resembled those of endocardium. In summary, the data demonstrate a marked heterogeneity of active membrane properties in canine ventricular muscle. These observations may aid in understanding the basis for rate-dependent changes in the T wave of the ECG, supernormal conduction in ventricular muscle, the greater sensitivity of epicardium to ischemia, and the rate dependence of some cardiac arrhythmias.

Correlation between effects of hydralazine on force and on the adenyl cyclase system of ventricular myocardium in dogs and cats.

Hydralazine is a potent arteriolar dilator, which increases cardiac output in patients with heart failure. Previous studies suggested that these beneficial effects might be due in part to a positive inotropic effect. The present study further investigated the effect of hydralazine on myocardial contractility and adenyl cyclase activity. In isolated cat papillary muscles, bath concentrations of hydralazine up to 10(-4) mol X litre-1 did not alter force development, whereas 10(-3) mol X litre-1 hydralazine increased isometric force by 31%. This effect was blocked by 10(-6) mol X litre-1 propranolol and was absent after catecholamine depletion produced by previous reserpine treatment. In canine ventricular myocardium hydralazine in all concentrations used (10(-7) to 10(-3) mol X litre-1) increased control adenyl cyclase activity. This increase was statistically significant in 10(-6) to 10(-3) mol X litre-1 concentrations, reaching a maximum of 69.5% at 10(-4) mol X litre-1. In cat ventricular myocardium 10(-6) to 10(-3) mol X litre-1 hydralazine increased the cyclic AMP production, although to a lesser magnitude than that in canine tissue. Hydralazine 10(-5) mol X litre-1 produced a 37.8% increase, and the maximum effect of 45.2% occurred at 10(-3) mol X litre-1. The positive effects of hydralazine were completely abolished by the addition of propranolol in dogs as well as in cats. Thus the adenyl cyclase stimulation induced by hydralazine is mediated through the beta receptor.(ABSTRACT TRUNCATED AT 250 WORDS)