Effects of neuropeptide Y (NPY) on mechanical activity and neurotransmission in the heart, vas deferens and urinary bladder of the guinea-pig

The effects of preincubation for 10 min with synthetic porcine neuropeptide Y (NPY) on muscle tone and autonomic transmission in the guinea-pig right atrium, vas deferens, urinary bladder, portal vein and trachea were analysed in vitro. NPY induced a metoprolol-resistant, long-lasting, positive inotropic and chronotropic effect per se in the spontaneously beating right atrium. Furthermore, NPY caused a reversible inhibition of both the metoprolol and atropine-sensitive auricle responses to field stimulation (2 Hz or 4 Hz for 2 s) without affecting the response to exogenous noradrenaline (NA) or acetylcholine (ACh). NPY did not induce any contraction of the vas deferens, but inhibited both the rapid twitch response and the sustained tonic contraction induced by field stimulation. The NPY-induced inhibition of the tonic contraction was more long-lasting than that of the twitch response. The tonic contraction was blocked by phentolamine and the twitch response by alpha-, beta-methylene ATP tachyphylaxis. NPY did not inhibit the contractile effects of NA, ATP or alpha-, beta-methylene ATP. NPY also induced a reversible reduction of the non-cholinergic, non-adrenergic contractile response to field stimulation of the urinary bladder. In the portal vein, NPY (up to 5 X 10(-7) M) did not inhibit the spontaneous motility or the phentolamine-sensitive contractile responses to field stimulation and NA. The atropine-sensitive contraction of the trachea or the non-adrenergic, non-cholinergic relaxation induced by field stimulation were not significantly influenced by NPY in doses up to 5 X 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)     

Occurrence and effects of endothelin in guinea-pig cardiopulmonary tissue

Endothelin-like immunoreactivity (-LI) was present in the guinea-pig cardiopulmonary tissues with the associated autonomic neural supply. The highest levels were found in the stellate ganglion (15 pmol g-1) followed by the vagus nerve, pulmonary artery, lung and right atrium of the guinea-pig. Endothelin I, but not endothelin III, induced an increase in contractile force and frequency followed by an atropine-resistant inhibition of right atrial contractility at higher concentrations. Exposure to endothelin I caused a pronounced, long-lasting coronary vasoconstriction as revealed by a decrease in perfusate outflow. In addition, both heart and contractile force were attenuated. Guinea-pig bronchi in vitro contracted upon exposure to endothelin I and III, but only endothelin I caused contraction of pulmonary arteries. The C-terminal hexapeptide of endothelin I did not influence right atrial, bronchial or pulmonary artery contractility. Endothelin I increased the mean arterial pressure and insufflation pressure and decreased the heart rate in the guinea-pig in vivo. In conclusion, endothelin-LI is present in the cardiovascular, respiratory and nervous tissues of the guinea-pig and endothelin induces strong coronary and pulmonary vasoconstrictor effects. The effects on atrial contractile force and frequency are concentration-dependent with stimulation at lower and inhibition at higher concentrations. Based on the diversity in response to endothelin III in the bronchi compared to atrium and pulmonary artery, it may be suggested that different receptor populations exist in bronchial and cardiovascular muscle, although the cellular localization and forms of endothelin present in guinea-pig cardiopulmonary tissue remain to be established.     

Mechanisms underlying pre- and postjunctional effects of neuropeptide Y in sympathetic vascular control

The effects of porcine neuropeptide Y (NPY) regarding sympathetic vascular control were studied in vitro on isolated rat blood vessels. The 10(-9)M NPY enhanced (about two-fold) the contractile responses to transmural nerve stimulation (TNS), noradrenaline (NA) and adrenaline (about two-fold) in the femoral artery. Higher concentrations of NPY (greater than 10(-8)M) caused an adrenoceptor-resistant contraction per se. The TNS-evoked [3H]NA efflux was significantly reduced by NPY in a concentration-dependent manner (threshold 10(-9)M). The calcium antagonist, nifedipine, abolished the contractile effects of NPY and the NPY-induced enhancement of NA contractions but did not influence the prejunctional inhibition of [3H]NA release. Receptor-binding studies showed that the ratio of alpha 1-to alpha 2-adrenoceptors in the femoral artery was 30:1. The NPY did not cause any detectable change in the number of alpha 1-or alpha 2-adrenoceptor binding sites or in the affinity of alpha 2-binding sites, as revealed by prazosin- and clonidine-binding, respectively. The NPY also inhibited the TNS-evoked [3H]NA release (by 42-86%) in the superior mesenteric and basilar arteries and in femoral and portal veins. The NPY still depressed TNS-evoked [3H]NA secretion from the portal vein in the presence of phentolamine. The NPY caused a clear-cut contraction in the basilar artery, increased the contractile force of spontaneous contractions in the portal vein, while only weak responses were observed in the superior mesenteric artery and femoral vein. The NA-induced contraction was markedly enhanced by NPY in the superior mesenteric artery, only slightly enhanced in the portal vein and uninfluenced in the femoral vein. In conclusion, in all blood vessels tested, NPY depresses the TNS-evoked [3H]NA secretion via a nifedipine-resistant action. Furthermore, NPY exerts a variable, Ca2+-dependent vasoconstrictor effect and enhancement of NA and TNS contractions.     

Guanethidine-sensitive release of neuropeptide Y-like immunoreactivity in the cat spleen by sympathetic nerve stimulation

Splenic nerve stimulation (10 Hz for 2 min) caused a perfusion-pressure increase, a volume reduction and an increase in the output of neuropeptide Y-like immunoreactivity (NPY-LI) from the isolated blood-perfused cat spleen. Gel-filtration HPLC analysis revealed that plasma NPY-LI collected during nerve stimulation was similar to the NPY-LI in the spleen and synthetic porcine NPY. Combined propranolol and phenoxybenzamine pretreatment enhanced NPY output upon nerve stimulation by about 60%. Forty percent of the perfusion-pressure increase and 25% of the volume reduction seen during control stimulations remained after adrenoceptor blockade. Guanethidine abolished the release of NPY-LI, the perfusion-pressure increase and the volume reduction normally seen upon splenic nerve stimulation. Infusion of synthetic porcine NPY caused a long-lasting increase in perfusion pressure and a relatively moderate volume reduction. Noradrenaline (NA) both increased perfusion pressure and induced a marked volume reduction. The NPY effects were resistant to adrenoceptor antagonists in doses which abolished the NA response. In conclusion, the present data show that NPY-LI is released upon sympathetic nerve stimulation by a guanethidine-sensitive mechanism. Furthermore, the sympathetic response is partially resistant to adrenoceptor antagonists and NPY has powerful vasoconstrictor effects. This provides further evidence for a role of NPY in sympathetic vascular control.     

Differential release of calcitonin gene-related peptide and neuropeptide Y from the isolated heart by capsaicin, ischaemia, nicotine, bradykinin and ouabain

The influence of various drugs as well as total ischaemia on the outflow of calcitonin gene-related peptide (CGRP), which is present in sensory nerves, and neuropeptide Y (NPY), which is co-stored with noradrenaline (NA), from the isolated guinea-pig heart, was studied in vitro. Capsaicin exposure and total ischaemia for 5-30 min induced a Ca2+-dependent increase in the outflow, suggesting release, of CGRP- but not NPY-like immunoreactivity (LI) from the heart. When characterized by high performance liquid chromatography (HPLC), the CGRP-LI present in heart extracts and the released CGRP-LI by capsaicin eluted in a major peak corresponding to synthetic CGRP. Incubation with morphine, indomethacin or reserpine pretreatment did not influence the capsaicin-evoked release of CGRP-LI. Capsaicin pretreatment depleted the cardiac content of CGRP-LI but not NPY-LI. The increase in perfusate volume observed after 30 min ischaemia in controls was reduced after capsaicin pretreatment. Nicotine exposure induced release of CGRP- as well as NPY-LI in a concentration- and Ca2+-dependent manner. The increased outflow of NPY-LI was not influenced by capsaicin pretreatment. Among other agents tested, bradykinin and ouabain caused increased outflow of CGRP but not of NPY-LI. Noradrenaline, tyramine, histamine, vasopressin, alpha,beta methylene ATP, ATP or adenosine induced changes in cardiac contractility or flow but did not evoke any detectable release of CGRP- or NPY-LI. In conclusion, the release of multiple neuropeptides can be studied in combination with contractile recordings using the isolated perfused guinea-pig whole heart preparation. Activation of cardiac sensory nerves by capsaicin, nicotine, bradykinin and ouabain, as well as ischaemia, induced release of CGRP while nicotine also evoked NPY release.     

Effects of neuropeptide Y (NPY) on isolated guinea-pig heart

Neuropeptide Y (NPY) is present in nerve fibres throughout the mammalian heart. We have elucidated the effects of NPY on the isolated papillary muscle and heart (Langendorff) from the guinea-pig. The paced papillary muscle was studied with regard to duration of the action potential, peak force, maximum rate of force development, time to peak force, and time from peak force to half relaxation; all these parameters were identical whether or not NPY (5 X 10(-7) M) was present in the medium. When a stimulation with trains of pulses was superimposed, the paced papillary muscle exhibited enhanced contractions. This increase in contractility was not observed in the presence of the beta-adrenoceptor antagonist propranolol (10(-6) M) and was thus considered to be adrenergically mediated. The latter (adrenergic) response was markedly attenuated by NPY. Since NPY did not interfere with the response to exogenous noradrenaline (NA) it is suggested that the peptide exerts a pre-junctional inhibitory affect on adrenergic nerve-mediated positive inotropy. Neuropeptide Y did not influence the electrocardiogram from the spontaneously beating heart (Lagendorff), nor did the peptide modify the positive chronotropic effect of exogenously applied NA. In conclusion, the results indicate that NPY is without effect on the heart muscle proper but that the sympathetic terminals of the heart possess pre-junctional receptors for NPY (and/or related peptides) related to suppression of stimulated NA release.     

Possible involvement of neuropeptide Y in sympathetic vascular control of canine skeletal muscle

Sympathetic nerve stimulation (2 min, 2 and 10 Hz) increased perfusion pressure in the blood perfused canine gracilis muscle in situ after pretreatment with atropine, desipramine and beta-adrenoceptor antagonists. This vasoconstriction was accompanied by clear-cut increases in the overflow of endogenous noradrenaline (NA) at both frequencies and, at 10 Hz but not at 2 Hz, also of neuropeptide Y-like immunoreactivity (NPY-LI). The irreversible alpha-adrenoceptor antagonist phenoxybenzamine enhanced the nerve stimulation induced overflows of NA and NPY-LI five- to eightfold and threefold, respectively. The fractional overflows of NA and NPY-LI per nerve impulse were similar in response to the high-frequency stimulation, indicating equimolar release in relation to the tissue contents of the respective neurotransmitter. The maximal vasoconstrictor response elicited by 10 Hz was reduced by about 50% following a dose of phenoxybenzamine which abolished the effect of exogenous NA and the remaining response was more long-lasting. Local i.a. infusion of NPY evoked long-lasting vasoconstriction in the presence of phenoxybenzamine, while the stable adenosine 5(1)-triphosphate (ATP) analogue alpha-beta-methylene ATP was without vascular effects. Locally infused NPY reduced the nerve stimulation evoked NA overflow by 31% (P less than 0.01) at 1 microM in arterial plasma, suggesting prejunctional inhibition of NA release. In conclusion, NPY-LI is released from the canine gracilis muscle upon sympathetic nerve stimulation at high frequencies. There is nerve stimulation evoked vasoconstriction, which is resistant to alpha-adrenoceptor blockade. This may in part be mediated by NPY released together with NA from the sympathetic vascular nerves.     

Calcitonin gene-related peptide: release by capsaicin and prolongation of the action potential in the guinea-pig heart

The mechanisms underlying the stimulatory effects of capsaicin on the contractility of the guinea-pig heart were studied in vitro. Capsaicin (10(-7) to 10(-5) M) caused an increased overflow of immunoreactive material, suggesting release of calcitonin gene-related peptide (CGRP)-and neurokinin A (NKA)-like immunoreactivity (-LI), but not of neuropeptide Y (NPY)-LI from the isolated Langendorff-perfused whole heart. The capsaicin-induced release was calcium-dependent. During exposure to capsaicin, the heart rate was increased, while the contractile force was reduced. In addition to releasing CGRP and NKA-LI, potassium (60 mM) also increased the overflow of NPY-LI. The potassium-induced release of peptides was less calcium-dependent than the response to capsaicin. Considerably higher tissue levels of CGRP-LI were found in the atria (about 30 pmol g-1) than in the ventricles (about 10 pmol g-1). In experiments on the right atria using transmembrane action-potential recordings of myocytes, CGRP induced a prolongation of the action potential concomitantly with an increase in rate and contractile force, which was similar to the effect of noradrenaline. Furthermore, CGRP increased the contractile force and relaxation velocity of the electrically stimulated atria. Capsaicin (10(-7) M) also increased the duration of the atrial action potential. In conclusion, CGRP-like material is released by capsaicin from the isolated guinea-pig heart. Both CGRP and capsaicin prolong the plateau phase of the action potential of atrial myocytes. Therefore, the present data give further evidence that CGRP release from sensory nerves within the heart underlies the cardiostimulatory actions of capsaicin.     

Effect of oral administration of nifedipine on neuropeptide Y- and noradrenaline-induced vasoconstriction in the human forearm

Neuropeptide Y (NPY) has recently been shown be co-released with noradrenaline (NA) from sympathetic nerves and to cause arterial vasoconstriction in experimental animals and man. The effect of a single oral dose (10 mg capsule) of nifedipine on NPY- and NA-induced reductions of forearm blood flow (FBF) was studied in seven healthy volunteers. Intra-arterial infusions of NPY and NA into the brachial artery before nifedipine caused dose-dependent reductions in FBF with threshold doses of 0.2 and 0.03 nmol x min-1, respectively. The response to NPY was slower in onset and more long lasting than that to NA. Forty-five min after administration of nifedipine, FBF and heart rate had increased significantly (by 49% and seven beats x min-1, respectively, P less than 0.001), while no significant change was observed in systemic blood pressure. The NPY-induced decrease in FBF was slightly but significantly attenuated after compared to before nifedipine (19 +/- 6 vs. 28 +/- 5% at 1.0 nmol NPY x min-1; P less than 0.01). The response to NA was, however, not significantly altered by nifedipine. In conclusion, the NPY-induced reduction in FBF in man was only slightly prevented and the NA response not significantly affected by oral nifedipine administration in a clinically used dose. This suggests that this calcium antagonist, in the present dosage, does not, to any major extent, inhibit the vasoconstrictor effect of NPY or NA in man in vivo.     

Inotropic, chronotropic, and arrhythmogenic effects of dopamine on the isolated working heart of rabbit

Some improvements of Kodama's method for perfusing the isolated rabbit heart in its working mode were made. Increases in the right and left atrium pressure, together with an increase in the pulmonary artery pressure, were observed to occur immediately after the start of venous return, and then all of the increased pressures were found to remain at each constant level. In these stable states, the administration of dopamine (DA) into the perfusate was found to produce dose-related increases in contractile activities. In the preparations denervated with reserpine or 6-hydroxydopamine, in which tyramine (Ty) produced no response, the inotropic effectiveness of DA did not differ from that in the normal ones. On the other hand, responses to noradrenaline (NA) were found to increase significantly after the denervation. DA produced a dose-related increase in heart rates in the normal preparation, and this effect was greatly suppressed in the denervated preparations, suggesting that the primary chronotropic effect of DA is an indirect one via the release of NA from the sympathetic nerve terminals. Arrhythmogenic effects of NA, Ty or DA were also observed in these preparations. At all the doses tested, the incidence rates by NA were as high as 50% or more, the type of arrhythmia being recognized as atrial or ventricular extrasystole from the ECG analysis. On the other hand, the rates by DA were relatively low, less than 34%. From a comparison of the incidence rates between the normal and denervated preparations, this effect of DA was considered to be primarily an indirect one.     

Reflex vascular responses to changes in left ventricular pressures, heart rate and inotropic state in dogs.

Dogs were anaesthetized with chloralose, artificially ventilated and the chests widely opened. Left ventricular mechanoreceptors, including those in or near the coronary arteries, were stimulated by changing the pressure in the aortic root. The pressures distending the left atrium and the aortic and carotid baroreceptors were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a hind limb and to the rest of the systemic circulation, which were perfused independently at constant flows. Physiological increases in peak left ventricular and coronary arterial pressures resulted in vasodilatation in both regions. These responses were not influenced by changes in the heart rate. Stimulation of the left cardiac sympathetic nerves resulted in increases in peak ventricular pressure and in the maximal rate of change of pressure (dP/dtmax). This also resulted in increases in perfusion pressures (vasoconstriction) at all levels of peak ventricular pressure although there was little effect on the responses to changes in ventricular pressure. Sympathetic stimulation had little effect on the relationship between perfusion pressures and aortic root pressure. Increases in ventricular filling also resulted in vasoconstriction at all levels of peak ventricular pressure. Increases in filling, however, did not affect the relationship between either perfusion pressure and aortic root pressure. Conversely, decreases in left ventricular filling, by bypassing some of the left atrial blood, resulted in vasodilatation at all levels of peak ventricular pressures but had no effect on the perfusion pressures at any aortic root pressure. The combination of sympathetic stimulation with decreased ventricular filling resulted in little effect on perfusion pressures or on their responses to changes in either aortic root or ventricular systolic pressures. We conclude that the vascular responses to stimulation of left ventricular mechanoreceptors are not enhanced by sympathetic stimulation, decreases in ventricular filling or the combination of the two. The apparent effects of each of these interventions alone on the relationships between perfusion pressures and ventricular, but not aortic root, pressure, could be explained if the receptors responsible were sensitive more to changes in aortic root and coronary arterial pressures than to pressure changes in the ventricle itself.     

Interaction of noradrenaline,NPY and VIP with the neurogenic cholinergic response of the rat uterine cervix in vitro

Quantitative pharmacological studies were performed on isolated uterine cervix which was obtained from oophorectomized and oestrogen-treated rats and therefore showed no spontaneous contractility. The concentration-response curves to ACh and carbacholine were to a varying degree depressed and right-shifted in the presence of NA, but not NPY or VIP. The electrically induced cholinergic contraction was potentiated in tissues from animals pretreated with reserpine or 6-OHDA, but only at high stimulation frequencies. Histochemically, both sympatholytics abolished NA from the cervical fibres, whereas immunoreactive NPY was still encountered. Tyramine in the organ bath reduced the contraction amplitude during electrical nerve stimulation concentration-dependently by a β-adrenoceptor-sensitive mechanism. In the presence of neostigmine the amplitude was reduced by NA, but not by NPY or VIP, which, on the other hand, had an inhibitory effect in the absence of neostigmine. The results offer further support for the view that, although the cervical smooth muscle cells are equipped with adrenoceptors, the neurogenic motor response at low stimulation frequencies (around 3 Hz) is mainly cholinergic. It appears that neurally released NA is able to influence these muscle cells primarily at high frequencies. There is no clear-cut evidence that the inhibitory effects of neural NPY or VIP on the cervix of spayed, oestrogen-treated rats are mediated by postjunctional receptors.     

Different effects of neuropeptide Y on electrically induced contractions in the longitudinal and circular smooth muscle layers of the female rabbit urethra

The effects of neuropeptide Y (NPY) on preparations of isolated longitudinal and circular smooth muscle from rabbit urethra were studied. In both types of muscle, electrically induced contractions and relaxations could be abolished by tetrodotoxin, (TTX). In the longitudinal muscle preparations the contraction was slightly reduced by prazosin, but markedly reduced by scopolamine and NPY. The NPY effect was not influenced by pretreatment with rauwolscine. Pretreatment with NPY had no effect on contractions induced by noradrenaline (NA) or carbachol and the peptide did not relax preparations contracted by these agents. In circular muscle an initial, fast response, not sensitive to prazosin or scopolamine was occasionally observed following electrical stimulation. A slow contraction component was regularly seen; this response was abolished by prazosin. Neuropeptide Y did not influence any of these responses. The preparations were concentration-dependently contracted by NA, whereas carbachol had no effect. Pretreatment with NPY did not affect contractions induced by NA, nor did the peptide relax NA-contracted preparations. In neither longitudinal nor circular muscle strips did NPY affect the electrically induced TTX sensitive relaxation of NA-contracted preparations. The results suggest that in the rabbit urethra NPY reduces contractions in the longitudinal muscle layer by selectively inhibiting the release of acetylcholine from cholinergic nerves. Neuropeptide Y did not appear to have any significant postjunctional effects nor to interfere with the release, or effects of NA or other transmitter agents. The physiological importance of the urethral effects of NPY remains to be established.     

Effects of myocardial contraction on coronary blood flow: An integrated model

The effects of myocardial contraction on the coronary flow are studied by means of an integrated structural model of left ventricular (LV) mechanics, coronary flow, and fluid and mass transport. This model relates global LV performance, and in particular coronary flow dynamics, to myocardial composition and structure and contractile sarcomere activity. Extravascular pressure is identified with hydrostatic tissue pressure,i. e., intramyocardial pressure (IMP), and is determined by the dynamics of myocardial contraction and fluid transport. Consistent with available experimental data, changes in myocardial function and contractile state are simulated by changing the sarcomere contractile properties or changing the LV loading conditions. The model's predictions are successfully compared with a wide range of experimental studies; all but one were performed at a constant coronary perfusion pressure and maximal vasodilation. The results indicate a domiant effect of the myocardial contractile state on coronary flow and a dissocation between coronary compression and LV cavity pressure (LVP) when the pressure is controlled by load changes. However, when active sarcomere contraction is regionally impaired by lidocaine, LVP plays an important role in the coronary flow characteristics. The model adequately predicts observations on the effect of cardiac contraction on systolic and diastolic coronary flows, as well as the role of LVP at different loading and contractile conditions. The analysis supports the hypothesis that coronary compression, as mediated through IMP, is independent of LV loading conditions and depends on myocardial contractility and coronary perfusion pressure.     

Biphasic nature of inotropic action of nitric oxide donor NOC7 in guinea-pig ventricular trabeculae.

The effects of nitric oxide (NO) donor on the contractility of guinea-pig ventricular trabeculae were explored to clarify whether NO affects the function of sarcoplasmic reticulum (SR) and the contractile elements. NO donor, 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), increased monotonically the amplitude of the twitch tension induced by electrical stimulation at a concentration of 20 microM. A higher concentration of NOC7 (200 microM) caused a biphasic response: transiently increased the amplitude of twitch and then decreased it. On wash-off of the higher concentration of NOC7, a rebound increase of the twitch amplitude was observed. An inhibitor of NO-sensitive guanylyl cyclase, 1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ), abolished the mono-tonic increase and rebound increase in the amplitude of tension but did not affect the decrease in the amplitude of tension at the higher concentration of NOC7. Oscillatory contractions developed by beta-escin-skinned muscle fibers were not changed by NOC7 at either concentration. Caffeine-induced tension transients indicating the Ca(2+)-accumulating and -releasing functions of intracellular Ca(2+) stores were not affected by NOC7. NOC7 did not change the steady tension developed in 1.6 microM Ca(2+) containing solution with and without ODQ. These results suggest that the biphasic inotropic effects by NOC7 were not caused by modifying the function of SR and the Ca(2+) sensitivity of myofilaments of the guinea-pig ventricular trabecula, but at least the positive inotropic effect was mediated through cGMP-dependent mechanisms.     

Renal effects of left atrial distension in dogs with chronic congestive heart failure.

The renal response to left atrial balloon inflation in normal dogs was compared with that in dogs with chronic congestive heart failure (CHF). CHF was induced by the production of an aortocaval fistula below the level of the renal arteries. CHF dogs showed elevated left ventricular end-diastolic pressure, enlarged hearts, a depression of myocardial contractility, pulmonary edema, ascites, and peripheral edema. They also showed significant decreases in urine flow, creatinine clearance, para-aminohippurate clearance, sodium and potassium excretion, fractional sodium excretion, osmolar clearance, arterial blood pressure, and heart rate. Balloon distension of the left atrium evoked a significant increase in urine flow and free-water clearance in the normal group. The reflex nature of this response was indicated by its blockade after bilateral cervical vagotomy. In contrast, the CHF group did not exhibit significant changes in urine flow or free-water clearance during balloon inflation. Plasma antidiuretic hormone (ADH) was significantly elevated in the CHF group; however, balloon distension reduced plasma ADH in both groups of dogs. Plasma renin activity was significantly elevated in the CHF dogs and was not changed by balloon distension in either group of dogs. It is concluded that animals with high-output CHF do not exhibit the atrial-diuretic reflex in spite of their ability to reduce ADH levels by atrial distension.     

Cross-talk between cardiac muscle and coronary vasculature

The cardiac muscle and the coronary vasculature are in close proximity to each other, and a two-way interaction, called cross-talk, exists. Here we focus on the mechanical aspects of cross-talk including the role of the extracellular matrix. Cardiac muscle affects the coronary vasculature. In diastole, the effect of the cardiac muscle on the coronary vasculature depends on the (changes in) muscle length but appears to be small. In systole, coronary artery inflow is impeded, or even reversed, and venous outflow is augmented. These systolic effects are explained by two mechanisms. The waterfall model and the intramyocardial pump model are based on an intramyocardial pressure, assumed to be proportional to ventricular pressure. They explain the global effects of contraction on coronary flow and the effects of contraction in the layers of the heart wall. The varying elastance model, the muscle shortening and thickening model, and the vascular deformation model are based on direct contact between muscles and vessels. They predict global effects as well as differences on flow in layers and flow heterogeneity due to contraction. The relative contributions of these two mechanisms depend on the wall layer (epi- or endocardial) and type of contraction (isovolumic or shortening). Intramyocardial pressure results from (local) muscle contraction and to what extent the interstitial cavity contracts isovolumically. This explains why small arterioles and venules do not collapse in systole. Coronary vasculature affects the cardiac muscle. In diastole, at physiological ventricular volumes, an increase in coronary perfusion pressure increases ventricular stiffness, but the effect is small. In systole, there are two mechanisms by which coronary perfusion affects cardiac contractility. Increased perfusion pressure increases microvascular volume, thereby opening stretch-activated ion channels, resulting in an increased intracellular Ca2+ transient, which is followed by an increase in Ca2+ sensitivity and higher muscle contractility (Gregg effect). Thickening of the shortening cardiac muscle takes place at the expense of the vascular volume, which causes build-up of intracellular pressure. The intracellular pressure counteracts the tension generated by the contractile apparatus, leading to lower net force. Therefore, cardiac muscle contraction is augmented when vascular emptying is facilitated. During autoregulation, the microvasculature is protected against volume changes, and the Gregg effect is negligible. However, the effect is present in the right ventricle, as well as in pathological conditions with ineffective autoregulation. The beneficial effect of vascular emptying may be reduced in the presence of a stenosis. Thus cardiac contraction affects vascular diameters thereby reducing coronary inflow and enhancing venous outflow. Emptying of the vasculature, however, enhances muscle contraction. The extracellular matrix exerts its effect mainly on cardiac properties rather than on the cross-talk between cardiac muscle and coronary circulation.     

Independent regulation of atrial coronary blood flow by atrial contraction rate in conscious dogs

Summary The effects of separate increases in atrial and ventricular contraction rates on the distribution of coronary flow within the heart were determined in conscious dogs with chronic heart block. Atrial tachycardia increased atrial blood flow and did not change ventricular blood flow. Ventricular tachycardia increased ventricular blood flow but not atrial blood flow. The results are consistent with the concept of local regulation of coronary perfusion by local myocardial energy turnover. The results also call attention to a potential adverse impact of atrial tachyarrhythmia in patients with underlying coronary ischemia.     

Role of Relative Changes in Caval Flows for Evaluation of Right Atrial Pressure Shifts Induced by Nitroglycerin

Experiments on cats treated with nitroglycerin showed dynamic relationship between changes in caval venous flows: blood flow increased in the superior vena cava and decreased in the inferior vena cava. Blood pressure in the right atrium either decreased, or increased. No significant changes in total venous return were observed during maximum shifts in right atrial pressure, while contractility of the right ventricular myocardium usually decreased. Our findings suggest that the direction of the right atrial pressure shifts induced by nitroglycerin does not depend on venous return, but is determined by the prevalence of flow changes in the superior vena cava or inferior vena cava.     

Neuropeptide Y (NPY) induced inhibition of preganglionic nerve stimulation evoked release of adrenalin and noradrenaline in the pithed rat

NPY, a peptide with 36 amino acid residues, is co-stored together with noradrenaline (NA) in cardiac and sympathetic perivascular nerves as well as with adrenalin (A) in adrenal chromaffin cells. NPY is released together with NA from sympathetic nerves and with A from the adrenal glands and appears to be involved in the control of sympathetic neurotransmission. The aim of the present study was to analyse the effect of NPY on the preganglionic nerve stimulation (PNS) evoked increases in plasma A and NA concentrations in pithed rats. In the first part of the study (I) only one PSN period (2 Hz for 45 s) was performed in each rat and the control group was compared to the NPY treated group. In the second part of the study (II) two PNS periods (1 Hz for 45 s) were performed in each rat, which either received saline or NPY before the second PNS. Thus, interindividual changes between the responses to the first and second PNS in control and NPY rats could be compared. In both study I and II, systemic infusion of NPY (2 micrograms kg-1 min-1 i.v.) significantly reduced the PNS-induced increase in plasma A by 26% and 42%, respectively (P less than 0.05). However, the increase in plasma NA elicited by PNS was significantly reduced only in study II by 23% (P less than 0.05). Infusion of NPY did not affect basal heart rate in either of the studies, but significantly increased basal blood pressure by about 10 mmHg. The blood pressure responses to PNS were significantly greater in NPY treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)