Academic literature on the topic 'SS-adrenoceptor'

Abstract Painful vaso-occlusive episodes in SCD are commonly associated with infection and other less definable stressors. Since epinephrine activates sickle red cell (SS RBC) adhesion in vitro, we studied the physiologic effect of adrenoceptor signaling activation by epinephrine on SS RBC adhesion to endothelium in vivo. We also investigated whether β-adrenoceptor blockade by propranolol would reduce adhesion and vaso-occlusion. Boluses of washed fluorescently labeled human SS RBCs, treated with epinephrine or vehicle in vitro, were infused into anesthetized athymic nude mice with window chambers implanted into their dorsal skin. Intravital microscopy of contralateral subdermal microvasculature was then performed to observe the dynamic interactions between flowing human SS RBCs and non-activated endothelium. Epinephrine induced human SS RBC adhesion, with frequent postcapillary obstruction. In contrast, neither sham-treated SS RBCs nor epinephrine-treated normal RBCs adhered appreciably to endothelium. Blood flow rates in venules of mice infused with epinephrine-treated SS RBCs was dramatically decreased, with fluxes of 19667±9048 and 6622±1494 circulating RBC/min/μm2 for sham-treated and epinephrine-treated cells, respectively (p=0.0074). SS RBC trapping in lung, spleen and kidney was assessed by fluorescence microscopy of frozen tissue sections collected 30 minutes post injection. Sham-treated SS RBCs were trapped to some degree in the lungs and spleen but only minimally in the kidney. However, epinephrine treatment markedly increased SS RBC trapping in all organs. To quantitate cell survival, sham-treated and epinephrine-treated SS RBCs labeled with different fluorescent dyes were co-infused into the same mouse. Blood samples were collected at intervals after infusion and analyzed by flow cytometry. Ten minutes after infusion, the percentage of circulating sham-treated SS RBCs was 3-fold higher than for epinephrine-treated cells, thus showing an inverse relationship between the percentage of circulating SS RBCs and the degree to which these cells were trapped in the organs studied. Finally, to determine whether propranolol can block epinephrine-induced SS RBC adhesion, SS RBCs were pretreated with propranolol, followed by treatment with epinephrine, then washed before infusion. Propranolol significantly inhibited the effect of epinephrine on SS RBC adhesion, resulting in markedly decreased obstruction of postcapillary vessels. Propranolol improved epinephrine-treated SS RBC circulation, with fluxes of 18809±7868, 3560±1443 and 16722±4985 circulating RBCs/min/μm2 for propranolol-treated, epinephrine-treated, and propranolol+epinephrine-treated cells, respectively (p<0.0001, propranolol-treated vs epinephrine-treated; p<0.0001, epinephrine-treated vs epinephrine+propranolol-treated). Ten minutes after infusion, the percentage of propranolol+epinephrine-treated SS RBCs in the circulation was similar to the percentage of propranolol-treated SS RBCs. Intravenous propranolol administration also blocked epinephrine-treated SS RBC adhesion, so that epinephrine-treated SS RBCs showed no increased adhesion in animals who received IV propranolol. We have thus demonstrated that (1) the stress hormone epinephrine can induce vaso-occlusion in vivo via activation of SS RBC adhesion, and (2) propranolol can inhibit epinephrine-induced SS RBC adhesion and prevent vaso-occlusion in this setting. Thus, we theorize that β-blockers may be useful in preventing or treating vaso-occlusion in SCD.

The mechanisms of cardiovascular control in the Antarctic fish Pagothenia borchgrevinki were investigated during rest and swimming exercise using pharmacological tools to reveal the nature of the control systems involved. Simultaneous and continuous recordings of ventral and dorsal aortic blood pressure, heart rate and ventral aortic blood flow (cardiac output) were made using standard cannulation procedures and a single-crystal Doppler flowmeter. Exercise produced a clear and consistent decrease in dorsal aortic blood pressure caused by a decrease in systemic vascular resistance. At the same time, ventral aortic blood pressure increased owing to the combined effects of a markedly increased cardiac output (by about 80 %) and branchial vasoconstriction. Judged from the effects of the alpha-adrenoceptor antagonist prazosin, control of the branchial vasculature involves an alpha-adrenoceptor-mediated vasoconstriction, in addition to more traditional cholinergic vasoconstrictor and ss-adrenoceptor-mediated dilatory mechanisms. The range of heart rates is large, from 3-4 beats min-1 in individual fish during hypertensive bradycardia to about 28 beats min-1 after atropine treatment. Both chronotropic and inotropic effects are responsible for a marked increase in cardiac output during exercise. The increase in blood pressure caused by adrenaline injection was due largely to an increase in cardiac output, while direct effects on the systemic vasculature were small and transient. The increase in cardiac output, in turn, was due solely to an adrenergic stimulation of stroke volume. A barostatic bradycardia, often seen in other vertebrates in response to adrenaline injection, was absent and it is possible that a decrease in heart rate was offset by direct adrenergic stimulation of the heart. Angiotensin II (Ang II) produced consistent hypertension by systemic vasoconstriction. In contrast to the effects of adrenaline injection, the hypertension caused by Ang II was accompanied by a marked bradycardia. This could be abolished by atropine, suggesting a cholinergic vagal reflex of the type found in other vertebrates. Angiotensin I also caused an elevated blood pressure, and this effect was abolished by the angiotensin converting enzyme inhibitor enalapril, demonstrating elements of an angiotensin-related cardiovascular control system.

We previously showed that lysozyme (Lzm-S), derived from leukocytes, caused myocardial depression in canine sepsis by binding to the endocardial endothelium to release nitric oxide (NO). NO then diffuses to adjacent myocytes to activate the cGMP pathway. In a canine right ventricular trabecular (RVT) preparation, Lzm-S also decreased the inotropic response to field stimulation (FSR) during which the sympathetic and parasympathetic nerves were simulated to measure the adrenergic response. In the present study, we determined whether the pathway by which Lzm-S decreased FSR was different from the pathway by which Lzm-S reduced steady-state (SS) contraction. Furthermore, we determined whether the decrease in FSR was due to a decrease in sympathetic stimulation or enhanced parasympathetic signaling. In the RVT preparation, we found that the inhibitory effect of Lzm-S on FSR was prevented by NO synthase (NOS) inhibitors. A cGMP inhibitor also blocked the depressant activity of Lzm-S. However, in contrast to the Lzm-S-induced decline in SS contraction, chemical removal of the endocardial endothelium by Triton X-100 to eliminate endothelial NO release did not prevent the decrease in FSR. An inhibitory G protein was involved in the effect of Lzm-S, since FSR could be restored by treatment with pertussis toxin. Atropine prevented the Lzm-S-induced decline in FSR, whereas β1- and β2-adrenoceptor function was not impaired by Lzm-S. These results indicate that the Lzm-S-induced decrease in FSR results from a nonendothelial release of NO. NO then acts through inhibitory G protein to enhance parasympathetic signaling.

Hypothesis: Excess SNS release of norepinephrine (NE) increases NCC activity, via an α1 adrenoceptor pathway, to drive the development and maintenance of salt-sensitive and neurogenic hypertension (HTN). Methods: Male Sprague-Dawley (SD) rats receiving a continuous s.c. saline or NE (600ng/min) infusion alone or in combination with terazosin (10mg/kg/day) were fed a 14-day 0.6% (NS) or 4% NaCl (HS) diet. Separate groups of male SD rats received a continuous s.c. NE infusion and 28-day NS or HS intake, on day 14 of HS a sub group of rats were switched to a co NE-terazosin s.c. infusion. Groups of male SHR rats received s.c. saline or terazosin for 14 days. Endpoint measurements (day 14 or 28) were basal MAP and NCC activity (peak natriuresis to iv hydrochlorothiazide (HCTZ; 2mg/kg) infusion and phosphoNCCT58 immunoblotting) and expression (via immunoblotting) was assessed (N=4/gp). Results: NE infused SD rats exhibit HTN and fail to suppress NCC expression and activity during HS-intake. α1-adreoceptor antagonism (confirmed pharmacologically) abolished the salt-sensitive component of NE HTN and restored dietary sodium evoked suppression of the NCC in NE infused SD rats. Critically, α 1 -adrenoceptor antagonism lowers BP and reduces NCC activity in established SHR HTN and restores sodium-evoked suppression of NCC activity and abolishes the salt sensitivity of BP in established NE-evoked SS HTN. Conclusion: SNS activation of the NCC by NE occurs in rat models of neurogenic and SS HTN. Our data demonstrates antagonism of α 1 -adrenoceptors lowers BP and NCC activity in established SS and neurogenic HTN and suggests α 1 -antagonists as a therapeutic option in sympathetically mediated HTN.

ObjectiveTo determine if the baseline baroreflex sensitivity (BRS) could be a useful predictor for the metoprolol therapeutic efficacy on postural orthostatic tachycardia syndrome (POTS) in children.MethodsIn this retrospective case-control study, 54 children suffering from POTS treated with metoprolol were recruited from the pediatric department of Peking University First Hospital. After 2–3 months of metoprolol treatment, all subjects were divided into responders and non-responders based on whether the symptom score (SS) was decreased by over 50% after metoprolol treatment at the follow-up. The baseline demographic parameters and the supine BRS during the head-up tilt test (HUTT) obtained by Finapres Medical System (FMS) were compared between the two groups. The value of BRS to predict the effectiveness of POTS was analyzed by a receiver-operating characteristic (ROC) curve.ResultsThe age, sex, height, weight, body mass index (BMI), course of the disease, baseline SS, medication time, metoprolol dose, and follow-up time of the subjects were not statistically different between the responders and non-responders (P &gt; 0.05). The decline in symptom scores (ΔSS) of the responders was more obvious than that of the non-responders (P &lt; 0.01). The supine BRS, BRS at maximum HR, supine heart rate (HR), and maximum HR were different between responders and non-responders (P &lt; 0.01, P = 0.022, P &lt; 0.01, P = 0.047). The binary multivariable analysis showed that baseline supine BRS was significantly associated with the response to metoprolol therapy [OR: 2.079, 95% CI: (1.077, 4.015), P = 0.029]. According to the ROC curve, the area under the curve (AUC) of baseline BRS was 0.912 (95% CI, 0.840–0.984), with a cut-off value of 8.045 ms/mmHg, yielding a sensitivity and specificity of 75.8% and 95.2%, respectively, in predicting the effectiveness of POTS.ConclusionThe baseline supine BRS level &gt; 8.045 ms/mmHg can predict a good therapeutic response to metoprolol and the results would assist in guiding the individualized β-adrenoceptor blocker use in pediatric patients suffering from POTS.