Contribution of Cardiovascular Reflexes to Differences in β-Adrenoceptor-Mediated Responses in Essential Hypertension

1981 ◽  
Vol 61 (s7) ◽  
pp. 177s-180s ◽  
Author(s):  
G. Jennings ◽  
A. Bobik ◽  
M. Esler ◽  
P. Korner
Keyword(s):  
Heart Rate ◽  
Essential Hypertension ◽  
Dose Range ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Normal Subjects ◽  
Cardiovascular Reflexes ◽  
Similar Dose ◽  
Before And After

1. The responses to stimulation of both cardiac and lymphocyte β-adrenoceptors were studied in 23 normal subjects and 23 with untreated essential hypertension. Lymphocyte cyclic adenosine monophosphate was measured in vitro after incubation with isoprenaline (0.01 μmol/l-10 mmol/l). There were no significant differences between the amount of cyclic adenosine monophosphate generated by lymphocytes in the two groups in the isoprenaline concentration range 0.01 μmol/l-1 mmol/l. 2. In the same subjects we compared cardiac β-adrenoceptor-mediated responses using the change in heart rate after bolus doses of isoprenaline (dose range 0.25–3 μg). In 12 subjects (six normotensive, six hypertensive) we studied the heart rate responses to isoprenaline before and after ‘total’ autonomic block (0.04 mg of atropine/kg and 300 μg of clonidine). The latter permitted assessment of intrinsic cardiac responsiveness after eliminating cardiovascular reflexes. 3. In subjects with reflexes intact the rise in heart rate was significantly greater in normal than in hypertensive subjects at all doses of isoprenaline. Isoprenaline evoked a similar dose-related fall in blood pressure in both groups, which contributed to the reflex drive. After autonomic block the differences in heart rate responses were no longer present. 4. The results indicate that the reduced tachycardia at a given dose of isoprenaline in hypertensive subjects is due to impairment in their baroreceptor—heart rate reflex since this was no longer present after atropine and clonidine. 5. The absence of any intrinsic difference in cardiac β-adrenoceptor responsiveness is in agreement with the results with lymphocytes.

DETERMINATION OF BLOOD CORTICOIDS USING THE IN VITRO RESIN UPTAKE OF 3H-PREDNISOLONE

1968 ◽  
Vol 57 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Hironori Nakajima ◽  
Mitsunori Murala ◽  
Masumitsu Nakata ◽  
Takeshi Naruse ◽  
Seiji Kubo
Keyword(s):  
Thyroid Function Test ◽  
Normal Subjects ◽  
Adrenal Function ◽  
Function Test ◽  
Before And After ◽  
Adrenal Response ◽  
Suppression Test

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.

Dobutamine Antagonizes Epinephrine's Biochemical and Cardiotonic Effects 

1998 ◽  
Vol 89 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Richard C. Prielipp ◽  
Drew A. MacGregor ◽  
Roger L. Royster ◽  
Neal D. Kon ◽  
Michael H. Hines ◽  
...  
Keyword(s):  
Artery Bypass ◽  
Phase 1 ◽  
Human Lymphocytes ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Production ◽  
Isobolographic Analysis ◽  
Camp Generation ◽  
Vitro Model

Background Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects. Methods The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10(-8) to 10(-4) M) or epinephrine (10(-9) M to 10(-5) M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 microg x kg(-1) x min(-1)) or epinephrine (10, 20, or 40 ng x kg(-l) x min(-1)), alone or in combination. Results In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration approximately 200%. However, when epinephrine (10(-6) M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10(-6) to 10(-4) M (P = 0.001). In patients, 1.25 to 5 microg x kg(-1) x min(-1) dobutamine increased the cardiac index (CI) 15-28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5microg x kg(-1) x mi(-1)) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 microg x kg(-1) x min(-1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects. Conclusions Dobutamine inhibits epinephrine-induced production of cAMP in human lymphocytes and appears to be subadditive by clinical and isobolographic analyses of the cardiotonic effects. These findings suggest that combinations of dobutamine and epinephrine may be less than additive.

scholarly journals The nucleoporin RanBP2 tethers the cAMP effector Epac1 and inhibits its catalytic activity

2011 ◽  
Vol 193 (6) ◽  
pp. 1009-1020 ◽  
Author(s):  
Martijn Gloerich ◽  
Marjolein J. Vliem ◽  
Esther Prummel ◽  
Lars A.T. Meijer ◽  
Marije G.A. Rensen ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Negative Regulator ◽  
Camp Signaling ◽  
Nuclear Pore ◽  
Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Wide Range

Cyclic adenosine monophosphate (cAMP) is a second messenger that relays a wide range of hormone responses. In this paper, we demonstrate that the nuclear pore component RanBP2 acts as a negative regulator of cAMP signaling through Epac1, a cAMP-regulated guanine nucleotide exchange factor for Rap. We show that Epac1 directly interacts with the zinc fingers (ZNFs) of RanBP2, tethering Epac1 to the nuclear pore complex (NPC). RanBP2 inhibits the catalytic activity of Epac1 in vitro by binding to its catalytic CDC25 homology domain. Accordingly, cellular depletion of RanBP2 releases Epac1 from the NPC and enhances cAMP-induced Rap activation and cell adhesion. Epac1 also is released upon phosphorylation of the ZNFs of RanBP2, demonstrating that the interaction can be regulated by posttranslational modification. These results reveal a novel mechanism of Epac1 regulation and elucidate an unexpected link between the NPC and cAMP signaling.

Ivabradine augments high-frequency dynamic gain of the heart rate response to low- and moderate-intensity vagal nerve stimulation under beta-blockade

2021 ◽  
Author(s):  
Toru Kawada ◽  
Hiromi Yamamoto ◽  
Kazunori Uemura ◽  
Yohsuke Hayama ◽  
Takuya Nishikawa ◽  
...  
Keyword(s):  
Heart Rate ◽  
Nerve Stimulation ◽  
High Frequency ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
Moderate Intensity ◽  
Beta Blockade ◽  
Hcn Channels

Our previous study indicated that intravenously administered ivabradine (IVA) augmented the dynamic heart rate (HR) response to moderate-intensity vagal nerve stimulation (VNS). Considering an accentuated antagonism, the results were somewhat paradoxical; i.e., the accentuated antagonism indicates that an activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels via the accumulation of intracellular cyclic adenosine monophosphate (cAMP) augments the HR response to VNS, whereas the inhibition of HCN channels by IVA also augmented the HR response to VNS. To remove the possible influence from the accentuated antagonism, we examined the effects of IVA on the dynamic vagal control of HR under beta-blockade. In anesthetized rats (n = 7), the right vagal nerve was stimulated for 10 min according to binary white noise signals between 0 and 10 Hz (V0-10), between 0 and 20 Hz (V0-20), and between 0 and 40 Hz (V0-40). The transfer function from VNS to HR was estimated. Under beta-blockade (propranolol, 2 mg/kg, i.v.), IVA (2 mg/kg, i.v.) did not augment the asymptotic low-frequency gain but increased the asymptotic high-frequency gain in V0-10 (0.53 ± 0.10 vs. 1.74 ± 0.40 beats·min−1·Hz−1, P < 0.01) and V0-20 (0.79 ± 0.14 vs. 2.06 ± 0.47 beats·min−1·Hz−1, P < 0.001). These changes, which were observed under a minimal influence from sympathetic background tone, may reflect an increased contribution of the acetylcholine-sensitive potassium channel (IK,ACh) pathway after IVA, because the HR control via the IK,ACh pathway is faster and acts in the frequency range higher than the cAMP-mediated pathway.

scholarly journals Thrombin-induced gap formation in confluent endothelial cell monolayers in vitro

Blood ◽  
1983 ◽  
Vol 62 (3) ◽  
pp. 549-556 ◽  
Author(s):  
M Laposata ◽  
DK Dovnarsky ◽  
HS Shin
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Gap Formation ◽  
Culture Dish ◽  
Cell Monolayers ◽  
Umbilical Vein Endothelial Cells

Abstract When thrombin is incubated with confluent monolayers of human umbilical vein endothelial cells in vitro, there is a change in the shape of the endothelial cells that results in gaps in the monolayer, disrupting the integrity of the endothelium and exposing the subendothelium. Using a grid assay to measure this phenomenon, we observed that up to 80% of the surface area once covered by cells was uncovered after a 15-min incubation with 10(-2) U/ml (10(-10)M) thrombin. The effect was apparent within 2 min and did not remove cells from the surface of the culture dish. The gaps in the monolayer completely disappeared within 2 hr after exposure to thrombin. The effect of thrombin was inhibited by preincubation of thrombin with hirudin or antithrombin III plus heparin or by preincubation of the monolayers with dibutyryl cyclic adenosine monophosphate (dbcAMP). Histamine also induced gap formation in endothelial cell monolayers. Both pyrilamine and cimetidine prevented the histamine-induced effect, but they had no effect on thrombin- induced gap formation. Intact monolayers were not disrupted by bradykinin, serotonin, C5a, or C3a. Our results suggest that small amounts of thrombin can induce repeated and transient exposure of the subendothelium, a situation believed to be conducive to atherogenesis and thrombosis.

scholarly journals A dual role for peripheral GDNF signaling in nociception and cardiovascular reflexes in the mouse

2019 ◽  
Vol 117 (1) ◽  
pp. 698-707 ◽  
Author(s):  
Luis F. Queme ◽  
Alex A. Weyler ◽  
Elysia R. Cohen ◽  
Renita C. Hudgins ◽  
Michael P. Jankowski
Keyword(s):  
Purinergic Receptor ◽  
Ischemia Reperfusion ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Response Element Binding ◽  
Dual Role ◽  
Cardiovascular Reflexes ◽  
Creb Binding Protein ◽  
Group Iii ◽  
Muscle Afferent

Group III/IV muscle afferents transduce nociceptive signals and modulate exercise pressor reflexes (EPRs). However, the mechanisms governing afferent responsiveness to dually modulate these processes are not well characterized. We and others have shown that ischemic injury can induce both nociception-related behaviors and exacerbated EPRs in the same mice. This correlated with primary muscle afferent sensitization and increased expression of glial cell line-derived neurotrophic factor (GDNF) in injured muscle and increased expression of GDNF family receptor α1 (GFRα1) in dorsal root ganglia (DRG). Here, we report that increased GDNF/GFRα1 signaling to sensory neurons from ischemia/reperfusion-affected muscle directly modulated nociceptive-like behaviors and increased exercise-mediated reflexes and group III/IV muscle afferent sensitization. This appeared to have taken effect through increased cyclic adenosine monophosphate (cAMP) response element binding (CREB)/CREB binding protein-mediated expression of the purinergic receptor P2X5 in the DRGs. Muscle GDNF signaling to neurons may, therefore, play an important dual role in nociception and sympathetic reflexes and could provide a therapeutic target for treating complications from ischemic injuries.

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