scholarly journals A Novel Alternative in the Treatment of Detrusor Overactivity? In Vivo Activity of O-1602, the Newly Synthesized Agonist of GPR55 and GPR18 Cannabinoid Receptors

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1384 ◽  
Author(s):  
Andrzej Wróbel ◽  
Aleksandra Szopa ◽  
Anna Serefko ◽  
Ewa Poleszak
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Detrusor Overactivity ◽  
Cannabinoid Receptors ◽  
Female Rats ◽  
Retinyl Acetate ◽  
Urine Production ◽  
Bladder Diseases ◽  
The Impact

The aim of the research was to assess the impact of O-1602—novel GPR55 and GPR18 agonist—in the rat model of detrusor overactivity (DO). Additionally, its effect on the level of specific biomarkers was examined. To stimulate DO, 0.75% retinyl acetate (RA) was administered to female rats’ bladders. O-1602, at a single dose of 0.25 mg/kg, was injected intra-arterially during conscious cystometry. Furthermore, heart rate, blood pressure, and urine production were monitored for 24 h, and the impact of O-1602 on the levels of specific biomarkers was evaluated. An exposure of the urothelium to RA changed cystometric parameters and enhanced the biomarker levels. O-1602 did not affect any of the examined cystometric parameters or levels of biomarkers in control rats. However, the O-1602 injection into animals with RA-induced DO ameliorated the symptoms of DO and caused a reversal in the described changes in the concentration of CGRP, OCT3, BDNF, and NGF to the levels observed in the control, while the values of ERK1/2 and VAChT were significantly lowered compared with the RA-induced DO group, but were still statistically higher than in the control. O-1602 can improve DO, and may serve as a promising novel substance for the pharmacotherapy of bladder diseases.

Modifying effects of the R389G β1-adrenoceptor polymorphism on resting heart rate and blood pressure in patients with obstructive sleep apnoea

2005 ◽  
Vol 110 (1) ◽  
pp. 117-123 ◽  
Author(s):  
Jan Börgel ◽  
Tino Schulz ◽  
Nina K. Bartels ◽  
Jörg T. Epplen ◽  
Nikolaus Büchner ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Obstructive Sleep Apnoea ◽  
Nervous Activity ◽  
Sleep Apnoea ◽  
Cpap Therapy ◽  
Pressure Therapy ◽  
Obstructive Sleep ◽  
Significant Difference ◽  
The Impact

OSA (obstructive sleep apnoea) stimulates sympathetic nervous activity and elevates resting HR (heart rate) and BP (blood pressure). In the present study in a cohort of 309 untreated OSA patients, the resting HR and BP during the daytime were correlated with AHI (apnoea/hypopnea index) and compared with patients with R389R (n=162), R389G (n=125) and G389G (n=22) genotypes of the β1-adrenoreceptor R389G polymorphism. We analysed the impact of the genotype on the decline of HR and BP in a subgroup of 148 patients (R389R, n=86; R389G, n=54; G389G, n=8) during a 6-month follow-up period under CPAP (continuous positive airway pressure) therapy during which cardiovascular medication remained unchanged. In untreated OSA patients, we found an independent relationship between AHI and resting HR (β=0.096, P<0.001), systolic BP (β=0.09, P=0.021) and diastolic BP (β=0.059, P=0.016). The resting HR/BP, however, did not differ among carriers with the R389R, R389G and G389G genotypes. CPAP therapy significantly reduced HR [−2.5 (−1.1 to −4.0) beats/min; values are mean difference (95% confidence intervals)] and diastolic BP [−3.2 (−1.5 to −5.0) mmHg]. The decline in HR was more significantly pronounced in the R389R group compared with the Gly389 carriers [−4.1 (−2.3 to −5.9) beats/min (P<0.001) compared with −0.2 (2.1 to −2.6) beats/min (P=0.854) respectively; Student's t test between groups, P=0.008]. Diastolic BP was decreased significantly (P<0.001) only in Gly389 carriers (R389G or G389G) compared with R389R carriers [−5.0 (−2.3 to −7.6) mmHg compared with −2.0 (0.4 to −4.3) mmHg respectively]. ANOVA revealed a significant difference (P=0.023) in HR reduction between the three genotypes [−4.1 (±8.4) beats/min for R389R, −0.5 (±9.3) beats/min for R389G and +1.9 (±7.2) beats/min for G389G]. In conclusion, although the R389G polymorphism of the β1-adrenoceptor gene did not influence resting HR or BP in untreated OSA patients, it may modify the beneficial effects of CPAP therapy on these parameters.

Cardiovascular Responding during Anger and Fear Imagery

1982 ◽  
Vol 50 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Richard J. Roberts ◽  
Theodore C. Weerts
Keyword(s):  
College Students ◽  
Blood Pressure ◽  
Heart Rate ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Scene Change ◽  
Emotional Responding ◽  
Analysis Of Change ◽  
Screening Interview

This study was designed to determine if visualization of anger- and fear-provoking scenes produced differential physiological patterns similar to those produced by in vivo manipulations. Normotensive college students were selected on the basis of their responses to newly developed Anger and Fear/Anxiety questionnaires and for their ability to construct arousing scenes during a screening interview. In a 2 × 2 design (intensity × emotion), four scenes (high and low anger, high and low fear) were constructed individually for each of 16 subjects to imagine. Diastolic blood pressure, systolic blood pressure, and heart rate were monitored during visualization of each scene. Change in diastolic blood pressure was significantly greater for high anger than for high fear as predicted. Analysis of change in heart rate and systolic blood pressure showed significant effects for intensity only. These results provide further support for the concept of physiological differentiation in human emotion and suggest the utility of imagery for systematic study of human emotional responding.

scholarly journals Do you mind if I take your blood pressure? Physical health monitoring of children and young people on ADHD medication amidst a pandemic

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S183-S184
Author(s):  
Emma Davies ◽  
Maham Khan ◽  
Claire Jones
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Young People ◽  
Physical Health ◽  
Health Monitoring ◽  
Neurodevelopmental Disorder ◽  
Adhd Medication ◽  
Children And Young People ◽  
Nice Guidance ◽  
The Impact

AimsTo establish whether physical health monitoring for CYP on ADHD medication is according to NICE guidance (2018).To determine the impact of COVID-19 pandemic restrictions on physical health monitoring for CYP on ADHD medication.Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, characterised by a persistent pattern of inattention and/or hyperactivity-impulsivity, directly impacting on academic, occupational, or social functioning. It affects between 1-5% of children and young people (CYP) most often presenting in early-mid childhood.Pharmacological treatment can be considered in CYP if certain criteria are met, where licensed medications include methylphenidate, dexamfetamine, lisdexamfetamine, atomoxetine and guanfacine. Stimulant and non-stimulant medications require frequent physical health monitoring due to their side effects including an increase in blood pressure and/or heart rate, loss of appetite, growth restriction and tics.MethodStandards and criteria were derived from the NICE guidance (2018), whilst local trust policies were reviewed, demonstrating discrepancies. Standards were expected to be met for 100% of patients.Electronic patient records were reviewed retrospectively from a representative cohort of CYP reviewed by clinicians in a community CAMHS service during March-November 2020. Data were entered manually into a spreadsheet for evaluation.ResultA total of 27 CYP records were reviewed, average age 13yo, on a range of stimulant/non-stimulant preparations.5 (19%) had height checked every 6 months, with 4 delayed to 7-8 months.For those >10yo, only 5 (19%) had weight checked every 6 months.Only 2 (7%) had their height and weight plotted on a growth chart and reviewed by the healthcare professional responsible for treatment.Just 4 (15%) had heart rate and blood pressure recorded before and after each dose change, whilst similarly only 4 (not the same) had these parameters recorded every 6 months.17 patients were reviewed by telephone/video call, where 5 patients provided physical health parameters (measured at home).ConclusionAcross all parameters, standards are not being met for the required physical health monitoring for CYP on ADHD medication.The COVID-19 pandemic has significantly changed the working conditions for community teams, impacting face to face reviews, creating challenges for physical health monitoring.Our ongoing implementations for change include the use of a proforma for physical health measurements, improving psychoeducation for families, exploring potential barriers with senior colleagues and collaborating with pharmacy colleagues to update local guidelines in accordance with the latest NICE recommendations. We aim to re-audit in June 2021.

Abstract 328: Hemodynamic Comparison of Zucker Diabetic Fatty Rats to Their Lean Littermates After Asphyxial Cardiac Arrest

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Claudius Balzer ◽  
Franz Baudenbacher ◽  
Michele M Salzman ◽  
William J Cleveland ◽  
Susan Eagle ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Arrest ◽  
Ejection Fraction ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Arterial Blood ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats ◽  
The Impact

Patients with metabolic syndrome are at higher risk for cardiac arrest (CA), and also have worse neurologic outcome after CA related to their comorbidities (e.g., Type 2 Diabetes Mellitus [T2DM]). Using Zucker Diabetic Fatty (ZDF) rats as a new and relevant model with common comorbidities for CA and cardiopulmonary resuscitation (CPR), we hypothesized that T2DM is associated with a lower chance for return of spontaneous circulation (ROSC) and/or a worse outcome regarding heart function after asphyxial CA compared to their lean littermates. Two groups of rats (8 ZDF, 7 lean) were monitored for 37±2 weeks. The rats were anesthetized and intubated; heart rate was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids and medications, respectively. Before ventilation was stopped to initiate asphyxial CA, rocuronium was given. After 8 minutes of CA, ventilation was re-initiated with FiO 2 1.0, epinephrine and sodium-bicarbonate were administered, and pneumatic chest compression were started with 200 compressions per minute. Chest compressions were stopped when a systolic blood pressure of 120 mmHg was achieved. During 4 hours of observation, vital parameters were closely monitored, blood gases were measured, and ejection fraction (EF %) was assessed with ultrasound. Data are mean ± SD. Statistics: Unpaired student’s t-test (two-tailed), α.05. At baseline, ZDF rats showed significantly higher blood glucose levels (504±52 vs 174±14 mg/dl) compared to their lean littermates. All ZDF and lean rats achieved ROSC, and measurements taken directly after ROSC and after the first hour showed no relevant differences. After four hours, there was no difference in heart rate between ZDF and lean rats. However, diabetic rats had a significantly higher mean arterial blood pressure (142±24vs. 107±19 mmHg) and ejection fraction (42±16%vs 20±8%) compared to their lean littermates. The hypothesis that ROSC-rate in diabetic rats would be lower could not be proven. Conversely, the ZDF rats showed a significantly higher blood pressure related to an increased EF%. Further analysis in this study will focus on the impact of T2DM on cardiac and neurological ischemia-reperfusion injury.

Measurement of sympathetic nerve activity in the unanesthetized rat

1989 ◽  
Vol 67 (1) ◽  
pp. 250-255 ◽  
Author(s):  
J. P. Fluckiger ◽  
G. Gremaud ◽  
B. Waeber ◽  
A. Kulik ◽  
A. Ichino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Blood Pressure Reduction ◽  
Response Curves ◽  
Nerve Activity ◽  
Dose Dependent

A new system was developed in our laboratory to continuously monitor intra-arterial pressure, heart rate, and sympathetic nerve activity in unanesthetized rats. The animals were prepared 24 h before the start of the experiments. Sympathoneural traffic was measured at the level of splanchnic nerve. The amplitude of the spikes recorded at this level was utilized to express sympathetic nerve activity. The amplitude of the residual electroneurogram signal present 30 min after the rats were killed was 32 +/- 2 mV (mean +/- SE; n = 11). For analysis, these background values were subtracted from values determined in vivo. The nerve we studied contains postganglionic fibers, since electrical activity decreased in response to ganglionic blockade with pentolinium (1.25 mg/min iv for 4 min). The amplitude of spikes fell by 43 +/- 4% (n = 4). Sympathetic nerve activity was highly reproducible at a 24-h interval (104 +/- 26 vs. 111 +/- 27 mV for the amplitude of spikes; n = 11). Dose-response curves to the alpha 1-stimulant methoxamine and to bradykinin were established in four rats. The increase in blood pressure induced by methoxamine caused a dose-dependent fall in sympathetic nerve activity, whereas the blood pressure reduction resulting from bradykinin was associated with a dose-dependent activation of sympathetic drive. These data therefore indicate that it is possible with out system to accurately measure sympathetic nerve activity in the awake rat, together with intra-arterial pressure and heart rate.

Neural mechanism underlying basilar arterial constriction by intracisternal L-NNA in anesthetized dogs

1993 ◽  
Vol 265 (1) ◽  
pp. H103-H107 ◽  
Author(s):  
N. Toda ◽  
K. Ayajiki ◽  
T. Okamura
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cerebral Arteries ◽  
Neural Mechanism ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Anesthetized Dogs ◽  
Arterial Constriction ◽  
Synthase Inhibitor

Basilar arterial diameters were angiographically measured in anesthetized dogs in which systemic blood pressure and heart rate were also monitored. Injections of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, into the cisterna magna produced a significant, persistent decrease in arterial diameter, the effect being reversed by intracisternal injections of L-arginine. The vasoconstrictor effect of L-NNA was diminished in dogs treated with hexamethonium. On the other hand, treatment with phentolamine in a dose sufficient to lower blood pressure to a level similar to that attained with hexamethonium did not inhibit, but rather potentiated, the effect of intracisternal L-NNA. Nicotine injected into the vertebral artery significantly dilated the basilar artery. The effect was abolished by treatment with L-NNA applied intracisternally, the inhibition being reversed by the addition of L-arginine. Systemic blood pressure and heart rate were not altered by intracisternally applied L-NNA and L-arginine. These findings support the hypothesis that basilar arterial constriction caused by intracisternal L-NNA is associated with a suppression of NO synthesis in nitroxidergic nerves innervating the cerebroarterial wall rather than an elimination of basal release of NO from the endothelium. Functional importance of nitroxidergic vasodilator innervation in cerebral arteries in vivo is thus clarified.

scholarly journals Vitamin D Receptor Activation Mitigates the Impact of Uremia on Endothelial Function in the 5/6 Nephrectomized Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
J. Ruth Wu-Wong ◽  
William Noonan ◽  
Masaki Nakane ◽  
Kristin A. Brooks ◽  
Jason A. Segreti ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Heart Rate ◽  
Vitamin D ◽  
Endothelial Function ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Receptor Activation ◽  
The Impact

Endothelial dysfunction increases cardiovascular disease risk in chronic kidney disease (CKD). This study investigates whether VDR activation affects endothelial function in CKD. The 5/6 nephrectomized (NX) rats with experimental chronic renal insufficiency were treated with or without paricalcitol, a VDR activator. Thoracic aortic rings were precontracted with phenylephrine and then treated with acetylcholine or sodium nitroprusside. Uremia significantly affected aortic relaxation (% in NX rats versus % in SHAM at 30 M acetylcholine). The endothelial-dependent relaxation was improved to –%, –%, and –% in NX rats treated with paricalcitol at 0.021, 0.042, and 0.083 g/kg for two weeks, respectively, while paricalcitol at 0.042 g/kg did not affect blood pressure and heart rate. Parathyroid hormone (PTH) suppression alone did not improve endothelial function since cinacalcet suppressed PTH without affecting endothelial-dependent vasorelaxation. N-omega-nitro-L-arginine methyl ester completely abolished the effect of paricalcitol on improving endothelial function. These results demonstrate that VDR activation improves endothelial function in CKD.

scholarly journals Human neuropeptide Y potentiates α1-adrenergic blood pressure responses in vivo

1998 ◽  
Vol 275 (3) ◽  
pp. H760-H766 ◽  
Author(s):  
Leander V. Schuerch ◽  
Lilly M. Linder ◽  
Eric Grouzmann ◽  
Walter E. Haefeli
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Neuropeptide Y ◽  
Blood Pressure Response ◽  
Human Hand ◽  
Response Curves ◽  
Fourfold Increase ◽  
Dose Rates ◽  
Blood Pressure Responses

Human neuropeptide Y (hNPY) potentiates the postjunctional vasoconstrictor effects of α1-adrenoceptor agonists in animals and in human hand veins in vivo. We therefore hypothesized that such an interaction might also occur in the human arterial bed. With the present single-blind cross-over study in 12 healthy volunteers, the effect of subpressor doses of hNPY on the blood pressure response to α1-adrenoceptor stimulation was evaluated. Dose-response curves were constructed to intravenously infuse phenylephrine with and without coinfusion with two different doses of hNPY (1.4 and 14.3 pmol ⋅ kg−1 ⋅ min−1). Blood pressure, heart rate, and forearm blood flow were recorded, and plasma hNPY was determined. During infusion of the higher hNPY dose, which increased hNPY from 24.0 ± 12.0 to 495.1 ± 12.6 pmol/l, blood pressure curves were 2.4-fold shifted toward lower phenylephrine dose rates ( P < 0.001). Forearm vascular resistance showed a similar trend, whereas the counterregulatory decrease of heart rate was similar in both groups. In contrast, the lower hNPY dose rate producing a fourfold increase in hNPY concentrations did not modify the response to phenylephrine. This in vivo study in humans demonstrates that hNPY induced potentiating effects on α1-adrenergic constriction also in the systemic arterial circulation and suggests that circulating hNPY may participate in the control of vascular tone.

Neither endogenous nor inhaled nitric oxide influences the function of circulating platelets in healthy volunteers

1999 ◽  
Vol 97 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Johanna ALBERT ◽  
N. Håkan WALLÉN ◽  
Nailin LI ◽  
Claes FROSTELL ◽  
Paul HJEMDAHL
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Healthy Volunteers ◽  
Thrombin Generation ◽  
Bleeding Time ◽  
Flow Cytometric ◽  
Fibrinogen Binding ◽  
Inhaled No

Experimental models have indicated prothrombotic effects of inhibition of nitric oxide (NO) production, and anti-thrombotic effects of inhaled NO, but the influence of NO on platelet function in vivo in humans is not well established. We therefore investigated the effects of systemic inhibition of NO synthesis by NG-monomethyl-⌊-arginine (⌊-NMMA) and of NO inhalation on platelet function in vivo. On two occasions, ⌊-NMMA (13.5 mg/kg) or saline infusion was administered to 14 healthy volunteers in a double-blind cross-over study. After a 30 min infusion of ⌊-NMMA or placebo, NO inhalation (30 p.p.m) was added during the remaining 30 min of infusion, on both occasions. Measurements included filtragometry ex vivo (reflecting platelet aggregability), flow-cytometric evaluation of platelets in whole blood (fibrinogen binding and P-selectin expression), plasma β-thromboglobulin (reflecting platelet secretion), cGMP in platelets and plasma, thrombin generation markers (thrombin fragment 1+2 and thrombin–antithrombin complexes) in plasma, and bleeding time. l-NMMA increased blood pressure and decreased heart rate. NO inhalation did not influence blood pressure or heart rate, but caused a 3-fold elevation in plasma cGMP levels (P < 0.001). Neither ⌊-NMMA nor NO influenced filtragometry readings or flow-cytometric determinations of platelet fibrinogen binding and P-selectin expression. Furthermore, plasma β-thromboglobulin, platelet cGMP and thrombin generation markers were not influenced by either treatment. Bleeding time was not influenced by ⌊-NMMA compared with placebo, but was increased by ≈ 25% during NO inhalation (P < 0.01), whether NO synthesis had been inhibited or not. The prolongation of bleeding time by inhaled NO was not accompanied by any effect on the platelet variables assessed. The present results indicate that circulating platelets are not influenced by endogenous or inhaled NO, presumably due to the rapid inactivation of NO in the blood. This does not exclude possible effects of endothelial NO in the interface between the blood and the vessel wall.

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