| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NEUROHUMORAL CONTROL OF CIRCULATION AND HYPERTENSION
1Department of Physiology, Institute for Medical Sciences, Jeonbug National University Medical School, Jeonju 561-180; and 2Department of Herbal Resources, Wonkwang University Professional Graduate School of Oriental Medicine, Iksan 570-749, Korea
Submitted 29 October 2002 ; accepted in final form 22 April 2003
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONDISCLOSURESREFERENCES |
|---|
atrial natriuretic peptide; histamine receptors; L-type calcium channels
Previously, it was shown that histamine H1 and H2 receptors are expressed in the atrium (18). Also, it was known that the heart contains as much as 3 µg histamine/g (13). Effects of histamine on the regulation of cardiac function are species specific and also tissue specific, even in the same animal. Histamine has been known to increase force of contraction in rabbit and human atria via activation of adenylyl cyclase, and to increase cAMP production (18, 28, 35). Both the positive inotropic effect and increase in cAMP production were blocked by cimetidine but not mepyramine, which indicates the effects are related to the activation of histamine H2 receptor (18). It was shown in the rabbit atria that the increase in contractility and cAMP production by histamine is caused exclusively by an activation of H2 receptor (17). Increase in intracellular cAMP production may increase Ca2+ influx via cAMP-dependent protein kinase A (PKA), which in turn may result in an increase in contractility (14, 31). It was shown that histamine-induced increase in Ca2+ current is blocked by H2-receptor antagonist cimetidine and PKA inhibitor RP-adenosine 3',5'-cyclic monophosphorothioate (RP-cAMP[S]) (19).
There are diverse reports on the effects of cAMP and Ca2+ in the regulation of ANP release. Increase in cAMP production by adenylyl cyclase activation with forskolin decreased atrial ANP release in perfused atria and hearts (7, 34). In contrast, it has also been shown that cAMP-elevating agents and cAMP analogs increase ANP secretion in cultured cardiac myocytes (5), sliced atria (1), isolated atria (36), and perfused heart (33). Diverse effects of Ca2+ on ANP release have also been reported: positive role of Ca2+ (33, 36) and negative inhibitory role of Ca2+ (9, 21, 23, 34). Hence, the present understanding of cAMP- or Ca2+-dependent regulation of ANP release is controversial.
In the present study, we propose the hypothesis that histamine may regulate atrial myocytic ANP release because 1) ANP stimulates histamine release from mast cells (30) and thus a reciprocal regulation may exist, 2) histamine elevates atrial cAMP levels (17, 18, 28, 35), and 3) evidence has been provided to suggest that an increase in cAMP modulates atrial ANP release (7). Because it was shown that acute stress induces cardiac mast cell activation and histamine release (20) and that histamine is involved in the coronary vasoconstriction (15), it is also possible to hypothesize that the ability of histamine to induce coronary vasoconstriction may, at least in part, be related to its ability to modulate ANP release. The purpose of the present study was to define the effect of histamine on atrial ANP release and to elaborate the receptors related to that and to disclose the postreceptor intracellular signaling.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONDISCLOSURESREFERENCES |
|---|
Experimental protocols. The atria were perfused for 60 min to stabilize ANP secretion. The atria were paced at 1.3 Hz. [3H]Inulin was introduced to the pericardial fluid 20 min before the start of the sample collection (3). The perfusate was collected at 2-min intervals at 4°C for analyses. Experiments were carried out by using six groups of atria to define receptor specificity (Fig. 1). Control cycles (two 12-min periods) were followed by histamine (group 1, 10 µM, n = 13; see Figs. 5A and 6) for 3 cycles (36 min). The effects were evaluated after two cycles (24 min) of administration of the agent. For the time-matched control, vehicle was introduced and values obtained during the periods corresponding to the control and experimental observations were compared (group 19, n = 10; see Fig. 6). One cycle (12 min) of infusion of histamine receptor subtype-selective antagonist was followed by an administration of histamine or vehicle in the presence of the prior agent. The following antagonists were used: 1) histamine H2-receptor antagonist cimetidine (group 2, 10 µM, n = 10, see Figs. 5A and 6; and group 3, n = 5, see Fig. 6); and 2) histamine H1-receptor antagonist triprolidine (group 4, 10 µM, n = 10, see Figs. 5B and 6; and group 5, n = 7, see Fig. 6). In another series of experiments, to define the effect of cell-permeable cAMP analog 8-Br-cAMP, control cycles (two 12-min periods) were followed by 8-Br-cAMP at 0.3 mM (group 6, n = 7; see Fig. 8), 0.6 mM (group 7, n = 9; see Figs. 7A and 8), 1.0 mM (group 8, n = 5; see Fig. 8), and vehicle (group 9, n = 6; see Fig. 8). In another series of experiments, to define involvement of L-type Ca2+ channels or protein kinases, three cycles (36 min) of infusion of inhibitors was followed by an infusion of histamine or vehicle in the presence of the prior agent. Control cycles (four 12-min periods) were followed by histamine (group 10, 1.0 µM, n = 9, Fig. 4; group 11, 10 µM, n = 10, Figs. 2A, 3, 4, 11, 13, and 15; group 12, 30 µM, n = 9, Fig. 4) for 3 cycles (36 min). The following inhibitors were used: 1) L-type Ca2+-channel inhibitor nifedipine (group 13, 1 µM, n = 7, Fig. 9A; and group 14, n = 6, Fig. 9B); 2) PKA inhibitors including KT5720 at 3 µM (group 19, n = 4, Fig. 13), 6 µM (group 20, n = 9, Figs. 12A, 13, 15; group 22, n = 5, Figs. 12B, 13 and 15), and 10 µM (group 21, n = 8, Fig. 13), and RP-cAMP[S] (group 23, RP-cAMP[S], 125 µM, n = 4, Figs. 14A and 15; and group 24, n = 3, Figs. 14B and 15); 3) the nonspecific protein kinase inhibitor staurosporine at 0.01 µM (group 15, n = 5, Fig. 11), 0.03 µM(group 16, n = 8, Fig. 11), and 0.1 µM(group 17, n = 7, Figs. 10A and 11; and group 18, n = 6, Figs. 10B and 11). The effects of histamine in the presence of modulating agent or vehicle were compared with the periods before and the third 12-min period after agonist. For the time-matched (group 25, n = 10, Figs. 2B, 4, 13, and 15) or modulating-agent control, values obtained during the periods corresponding to the control and experimental observations were compared.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Radioimmunoassay of ANP. Immunoreactive ANP in the perfusate was measured by a specific radioimmunoassay, as described previously (3). The secreted amount of immunoreactive ANP was expressed as nanogram of ANP per minute per gram of atrial tissue. The molar concentration of immunoreactive ANP in terms of the ECF translocation reflects the concentration of ANP in the interstitial space of the atrium and, therefore, indicates the rate of myocytic release of ANP into the surrounding paracellular space (2, 3). It was calculated as ANP released (in µM) = immunoreactive ANP (in pg·min-1·g-1)/ECF translocated (in µl·min-1·g-1)·3,063 [molecular weight of ANP-(1-28)]. Most of the ANP secreted is processed ANP (3).
Radioimmunoassay of cAMP. cAMP was measured by equilibrated radioimmunoassay (6, 7). Briefly, standards and samples were taken up in a final volume of 100 µl of 50 mM sodium acetate buffer (pH 4.8) containing theophylline (8 mM), and then 100 µl of diluted cAMP antiserum (Calbiochem-Novabiochem, San Diego, CA) and iodinated 2'-O-monosuccinyl-adenosine 3',5'-cyclic monophosphate tyrosyl methyl ester ([125I]ScAMP-TME; 10,000 cpm/100 µl) were added and incubated for 24 h at 4°C. For the acetylation reaction, 5 µl of a mixture of acetic anhydride and triethylamine (1:2) was added to the assay tube before the addition of antiserum and tracer. The bound form was separated from the free form by charcoal suspension. [125I]ScAMP-TME was prepared as described previously (6, 38). Radioimmunoassay for cAMP was done on the day of experiments, and all samples from one experiment were analyzed in a single assay. Nonspecific binding was <2.0%. The 50% intercept was at 16.5 ± 0.79 fmol/tube (n = 10). The intra- and interassay coefficients of variation were 5.0 (n = 10) and 9.6% (n = 10), respectively. Nonspecific value of the buffer solution was subtracted from the value of atrial perfusate. The amount of cAMP efflux was expressed as pmol cAMP per minute per gram of atrial tissue. The molar concentration of cAMP efflux in terms of ECF translocation, which may reflect the concentration of cAMP in the interstitial space fluid (2, 3, 6), was calculated as cAMP efflux (in µM) = cAMP (in pmol· min-1·g-1)/ECF translocated (in µl·min-1·g-1).
For the preparation of perfusates, 100 µl of the perfusate were treated with trichloroacetic acid (900 µl) for a final concentration 6% for 15 min at room temperature and were centrifuged at 4°C. The supernatant (500 µl) was transferred to a polypropylene tube, extracted with water-saturated ether (1 ml) three times, and then dried by using a SpeedVac concentrator (Savant, Farmingdale, NY). The dried samples were resuspended with sodium acetate buffer.
Statistical anaysis. Significant difference was compared by using repeated-measures ANOVA followed by Bonferroni's multiple-comparison test (Figs. 2, 5, 7, 9, 10, 12, and 14). Student's t-test for unpaired data (Figs. 4, 6, 8, 11, 13, and 15) was also applied. Correlation coefficients were determined with the use of linear regression analysis. Statistical significance was defined as P < 0.05. The results are given as means ± SE.
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONDISCLOSURESREFERENCES |
|---|
18 min and was then maintained thereafter
(Figs. 2, Aa and
Ac, and
3A). However,
histamine-induced increase in atrial dynamics showed a peak response and waned
(Fig. 2, Af and
Ag). Decrease in atrial myocytic ANP release by histamine
was coincident with an increase in cAMP production
(Fig. 3A) and was a
function of atrial cAMP production (Fig.
3B). Because the binding of histamine to H2
receptor triggers an early specific response characterized by an increase in
cAMP levels, we analyzed early responses to define the relationship between
cAMP and ANP release. Before histamine, ANP concentration was 0.530 ±
0.073 µM and decreased by 50.69 ± 4.50% (mean of the last two
periods) to 0.249 ± 0.036 µM after three cycles of histamine
(Fig. 4). The effects of
histamine on ANP release, cAMP production, and atrial dynamics were
concentration-dependent (Fig.
4). For the time-matched control, changes in ANP secretion, ECF
translocation, ANP concentration, cAMP production, and atrial dynamics were
constant and stable (Fig.
2B). The responses were reproducible during the periods
corresponding to the control and experimental observations (differences
between the periods were not significant; n = 10). Histamine decreases ANP release via H2 receptor. To define the receptor responsible for the effect of histamine on the regulation of ANP release, an antagonist of the histamine H2 receptor was applied. An inhibition of histamine H2 receptor with cimetidine completely blocked all effects of histamine on ANP release, cAMP production, and atrial dynamics (Figs. 5A and 6). Group for the experiment of histamine shown in Fig. 5A is different from that of Fig. 2. The effects of histamine were very similar in both groups. Cimetidine alone did not show significant changes in the above atrial parameters (Fig. 6). In contrast to the H2-receptor antagonist, the H1-receptor antagonist triprolidine did not block the histamine-induced decrease in ANP release and increase in atrial dynamics (Figs. 5B and 6). In the presence of triprolidine, histamine increased cAMP production significantly, but the response was slightly attenuated (Fig. 5B). At the peak difference of the second cycle of histamine in the presence of triprolidine, the differences over the mean of the two periods before histamine were significant between the presence and absence of triprolidine (in difference in percent changes, 80.74 ± 19.37% for triprolidine plus histamine, n = 9 vs. 187.02 ± 33.90% for histamine, n = 13; P < 0.05). Triprolidine alone did not significantly affect the cAMP concentration (0.072 ± 0.013 µM for triplolidine vs. 0.050 ± 0.007 µM for control period, n = 7; P < 0.05). Triprolidine alone decreased ANP release at the later phase of the treatment and increased atrial dynamics at the early phase slightly but significantly (Fig. 6).
8-Br-cAMP mimicks the effect of histamine on ANP release. To define the role of cAMP in the regulation of ANP release, a cell-permeable cAMP analog, 8-Br-cAMP, was infused. 8-Br-cAMP decreased ANP secretion and ANP release (Fig. 7, Aa and Ac). 8-Br-cAMP increased atrial stroke volume and pulse pressure (Fig. 7, Ad and Ae). 8-Br-cAMP decreased ANP release and increased atrial dynamics in a dose-dependent manner (Fig. 8, A and B). As shown in Fig. 7B, KT5720, a PKA selective inhibitor, blocked 8-Br-cAMP-induced decrease in ANP release and increase in atrial dynamics [ANP concentration (in µM): -4.28 ± 3.48, n = 4, vs. -39.72 ± 2.30, n = 9; P < 0.001].
Inhibition of L-type Ca2+ channel with nifedipine failed to change histamine-induced decrease in ANP release. Because the H2 receptor-activated increase in cAMP production is expected to increase Ca2+ influx via L-type Ca2+ channels (19), and increase in Ca2+ influx via L-type channel is an inhibitory regulator for ANP release (9, 21, 34, 39), the effect of Ca2+ channel blockade on histamine-induced decrease in ANP release was tested. Nifedipine, an inhibitor of L-type Ca2+ channel, increased ANP release with a concomitant decrease in atrial dynamics (Fig. 9, Aa, Ac, Af, Ag, Ba, Bc, Bf, and Bg). The effects of nifedipine were stable and maintained during the periods of experiments. Nifedipine decreased ECF translocation slightly but significantly, which was coincident with a decrease in atrial dynamics (Fig. 9, Ab and Bb). Nifedipine had no significant effect on cAMP efflux (Fig. 9, Bd and Be). In the presence of nifedipine, histamine decreased ANP release concomitantly with an increase in cAMP efflux (Fig. 9, Aa and Ac–Ae). Nifedipine failed to change histamine-induced decrease in ANP release (in difference in percent changes, -41.79 ± 4.34% for nifedipine plus histamine, n = 7 vs. -50.69 ± 4.50% for histamine, n = 10; P < 0.05). Nifedipine attenuated histamine-induced increase in atrial stroke volume and pulse pressure (Fig. 9, Af and Ag).
Protein kinase inhibitor staurosporine blocks histamine-induced decrease in ANP release. As shown in Fig. 10, staurosporine (0.1 µM) slightly but not significantly decreased atrial ANP release (Fig. 10, Aa, Ac, Ba, and Bc). Staurosporine significantly decreased atrial dynamics (Fig. 10, Af, Ag, Bf, and Bg). In the presence of staurosporine, histamine-induced decrease in ANP release was not observed (Figs. 10, Aa and Ac, and 11). Staurosporine (0.03 µM) attenuated histamine-induced decrease in ANP release (Fig. 11). Staurosporine attenuated histamine-induced decrease in ANP release in a concentration-dependent manner. The change in ANP concentration by staurosporine (0.1 µM) plus histamine was not significantly different from those by staurosporine alone. Staurosporine blocked histamine-induced increase in atrial dynamics (Fig. 10, Af and Ag). Histamine induced a slight but not significant increase in ANP secretion (Fig. 10Aa), which may be related with an increased ECF translocation. In the presence of staurosporine, histamine significantly increased cAMP production (Fig. 10, Ad and Ae). Histamine-induced increase in cAMP concentration was not different between the presence and absence of staurosporine (232.94 ± 59.71% for staurosporine, 0.1 µM, plus histamine, n = 7, vs. 220.93 ± 54.39% for histamine, n = 10; P < 0.05). Staurosporine significantly shifted the relationship between cAMP and ANP release (in changes in slopes; -0.035 ± 0.023 for staurosporine plus histamine, n = 6 vs. -0.133 ± 0.024 for histamine, n = 10; P < 0.05).
Because the histamine-induced decrease in ANP release was found to be a function of increase in cAMP efflux and also staurosporine blocked the response, involvement of PKA activity was defined. KT5720 (6 µM) decreased ANP secretion and ANP concentration slightly but significantly concomitantly with a decrease in atrial dynamics (Fig. 12, Aa, Ac, Af, Ag, Ba, Bc, Bf, and Bg). KT5720 alone did not significantly influence cAMP efflux. KT5720-induced changes were stable after the third cycle (Figs. 12B and 15). In the presence of KT5720, histamine decreased ANP release, but the response was significantly attenuated (Figs. 12, Aa and Ac, and 15). In the presence of KT5720, histamine increased cAMP efflux significantly, but the response was attenuated. Difference in percent changes in cAMP concentration induced by histamine was not significantly different between the presence and absence of KT5720 (194.66 ± 57.08% for KT5720 plus histamine, n = 9 vs. 220.93 ± 54.39% for histamine, n = 10; P < 0.05). However, KT5720 attenuated histamine-induced accentuation of cAMP concentration in the absolute amount of changes (0.040 ± 0.007 µM for KT5720 plus histamine, n = 9 vs. 0.089 ± 0.013 µM for histamine, n = 10; P < 0.01). KT5720 attenuated histamine-induced increase in atrial stroke volume and pulse pressure. A lower concentration of KT5720 (3 µM) failed to modulate histamine-induced decrease in ANP release (Fig. 13). Up to 10 µM of KT5720, the attenuation by KT5720 of the histamine-induced decrease in ANP release was not different from that by 6 µM of KT5720 (Fig. 13). RP-cAMP[S], another structurally different PKA inhibitor, did not significantly influence ANP release and atrial dynamics (Figs. 14B and 15). In the presence of RP-cAMP[S], histamine decreased ANP secretion and ANP concentration, but the response was attenuated (Figs. 14, Aa and Ac, and 15). RP-cAMP[S] attenuated histamine-induced accentuation of atrial dynamics (Figs. 14, Ad and Ae, and 15). In this experiment, the response of cAMP could not be determined because the specific antiserum for the radioimmunoassay cross-reacted with RP-cAMP[S].
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONDISCLOSURESREFERENCES |
|---|
Histamine decreases ANP release via H2-receptor activation. Histamine results in a decrease in ANP release as well as increases in cAMP production and atrial dynamics in a concentration-dependent manner. The histamine H2- but not H1-receptor antagonist blocked effects of histamine. Triprolidine, a H1-receptor antagonist did not block histamine-induced changes in ANP release, cAMP production and atrial dynamics. Previously, Hattori et al. (18) showed in rabbit atria that histamine-induced accentuation of atrial dynamics is exclusively mediated by H2 receptor. They also showed that H2-receptor activation with histamine increased cAMP production in rabbit atria. The present data are in agreement with the report. The present study suggests that increase in atrial cAMP production by H2-receptor activation is related to the histamine-induced decrease in ANP release. In the present study, it was shown that triprolidine alone slightly but significantly increased atrial dynamics and decreased ANP release. Triprolidine attenuated histamine-induced accentuation of cAMP production. The mechanism by which triprolidine elicits the effects is not clear at present.
Mechanism by which H2-receptor activation regulates ANP release. The present study shows for the first time that an activation of G protein-coupled histamine H2 receptor decreases atrial ANP release via cAMP-protein kinase signaling. Histamine-induced decrease in ANP release was a function of cAMP production. Because an accentuation of cAMP production results in an activation of L-type Ca2+ channels (14, 19, 31) and also an increase in Ca2+ influx via L-type channels inhibits ANP release in the beating atria and perfused heart (9, 21, 34, 39), it was expected to observe a role for increased Ca2+ influx in the cAMP inhibition of ANP release by histamine. However, histamine-induced decrease in ANP release was not modified by an L-type Ca2+ channel inhibitor, nifedipine. An increase in ANP secretion by an L-type Ca2+ channel inhibitor is consistent with the previous report (39). Nifedipine blocked histamine-induced accentuation of atrial dynamics. This is consistent with previous reports (14, 19, 31).
A protein kinase nonselective inhibitor, staurosporine, blocked histamine-induced decrease in ANP release in a concentration-dependent manner. In this condition, histamine increased atrial cAMP production. Furthermore, PKA selective inhibitors attenuated histamine-induced decrease in ANP release. This latter seems likely that histamine-induced decrease in ANP release may partly be related to PKA activation. Also, the finding that cell-permeable cAMP analog decreases ANP release and that the effect is blocked by KT5720 indicates that cAMP inhibits ANP release via a PKA-dependent pathway. Taken together, these results suggest that histamine decreases ANP release by H2 receptor-cAMP signaling via PKA-dependent and -independent pathways. Previously, it was shown that forskolin decreased ANP release via cAMP-protein kinase signaling in which forskolin-induced decrease of ANP release was a function of an accentuation of cAMP production (7). The present data are consistent with the previous report. PKA selective inhibitors attenuated histamine-induced accentuation of atrial dynamics.
The PKA-selective inhibitor KT5720 significantly inhibited histamine-induced increase in cAMP concentration in absolute amount but not in difference in percent changes. The mechanism by which KT5720 decreases stimulated cAMP efflux by H2-receptor activation is unknown at present. It was previously shown that forskolin-induced accentuation of cAMP production was not modulated by protein kinase nonselective and PKA selective inhibitors staurosporine and KT5720, respectively (7). Therefore, it is suggested that the site of modulation by protein kinase inhibitor of the histamine-induced increase of cAMP concentration is upstream of the adenylyl cyclase. However, histamine H2-receptor desensitization may not be involved in this process, because desensitization of G protein-coupled receptor is known to be related with phosphorylation of the receptor by PKA activation (16, 27) and also because PKA is reported not to be involved in the H2-receptor desensitization (10, 26, 37).
Taken together, the present study suggests that histamine decreases atrial ANP release via L-type Ca2+ channel-independent and PKA-dependent and -independent signaling. This is consistent with the hypothesis that an increase of Ca2+ influx by H2-receptor activation by histamine is mainly involved in the control of atrial dynamics but not in the regulation of ANP release. Therefore, these data suggest that an activation of G protein-coupled histamine H2 receptor of the cardiac atrium inhibits secretory function via cAMP-protein kinase signaling and accentuates atrial dynamics via cAMP-Ca2+ channel pathway. This notion is in relation with the previous report that showed a Ca2+ channel-independent and cAMP-protein kinase-dependent signaling for forskolin-induced inhibition of ANP release (7).
Previously, it was shown that cAMP-elevating agents increased ANP secretion in cultured cardiac myocytes (5), isolated atria (1, 36), or perfused hearts (33). The present data contrast with these reports. The discrepancy between the present study and previous reports may be related to the methodology. The most important stimulus for the regulation of ANP secretion is atrial stretch (11, 24). We have shown that ANP secretion is regulated by a two-step sequential mechanism (2, 3). First, ANP is released from atrial myocytes into the surrounding extracellular space. Second, convective transendocardial translocation of the ANP-containing ECF into the bloodstream is induced by atrial contraction. The convective translocation of the ECF as the final step of ANP secretion was shown to be dependent on the atrial workload. Therefore, an increase in atrial workload would be expected to accentuate ANP secretion by increasing the translocation of ECF. Recently, it was also shown that atrial workload inversely determined the size of extracellular space (4). The latter directly determined the translocation of the ECF in terms of atrial workload. Therefore, it is suggested that the size of extracellular space and also atrial workload are important in the regulation of the translocation of ECF and released ANP. This may also be implicated in the cultured cardiocytes. This notion may be relevant to the discrepancy between the present study and previous reports.
Recently, it was shown that acute stress induces cardiac mast cell activation and histamine release (20). Also, it has been known that cardiac mast cell-derived histamine can constrict coronary artery (15). Therefore, the present study showing histamine-induced decrease in ANP release implicates the pathophysiology of cardiac diseases accompanying cardiac mast cell activation (22). In such a pathological condition as that mentioned above, which accompanies mast cell activation and increase in histamine release, histamine-induced decrease in ANP release may aggravate the coronary dysfunction. Because ANP is known to vasodilate the coronary vasculature, we propose that histamine-induced decrease in ANP release may, at least in part, lead to impaired coronary vasodilation.
In summary, the present study shows that an activation of histamine H2 receptor adenylyl cyclase-coupled receptor by histamine decreases atrial ANP release, in which an elevation of cAMP production regulates ANP release via cAMP-protein kinase signaling.
|
DISCLOSURES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONDISCLOSURESREFERENCES |
|---|
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONDISCLOSURESREFERENCES |
|---|
1-adrenoceptor
blockade sensitizes the H1 and H2 receptor systems in
human atrium: role of cyclic nucleotides. Naunyn Schmiedebergs Arch
Pharmacol 353:
661–670, 1996.[Web of Science][Medline]
This article has been cited by other articles:
|
|
 |
|
  D. A. Heaton, D. Li, S. C. Almond, T. A. Dawson, L. Wang, K. M. Channon, and D. J. Paterson Gene Transfer of Neuronal Nitric Oxide Synthase into Intracardiac Ganglia Reverses Vagal Impairment in Hypertensive Rats Hypertension, February 1, 2007; 49(2): 380 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Heaton, M. Lei, D. Li, S. Golding, T. A. Dawson, R. M. Mohan, and D. J. Paterson Remodeling of the Cardiac Pacemaker L-Type Calcium Current and Its {beta}-Adrenergic Responsiveness in Hypertension After Neuronal NO Synthase Gene Transfer Hypertension, September 1, 2006; 48(3): 443 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Dietz Mechanisms of atrial natriuretic peptide secretion from the atrium Cardiovasc Res, October 1, 2005; 68(1): 8 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Jin, J. F. Wen, D. Li, and K. W. Cho Osmoregulation of atrial myocytic ANP release: osmotransduction via cross-talk between L-type Ca2+ channel and SR Ca2+ release Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1101 - R1109. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
%, percent
change.
